PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (619983)

Clipboard (0)
None

Related Articles

1.  Cardiovascular magnetic resonance imaging of isolated perfused pig hearts in a 3T clinical MR scanner 
Purpose
An isolated perfused pig heart model has recently been proposed for the development of novel methods in standard clinical magnetic resonance (MR) scanners. The original set-up required the electrical system to be within the safe part of the MR-room, which introduced significant background noise. The purpose of the current work was to refine the system to overcome this limitation so that all electrical parts are completely outside the scanner room.
Methods
Four pig hearts were explanted under terminal anaesthesia from large white cross landrace pigs. All hearts underwent cardiovascular magnetic resonance (CMR) scanning in the MR part of a novel combined 3T MR and x-ray fluoroscopy (XMR) suite. CMR scanning included real-time k-t SENSE functional imaging, k-t SENSE accelerated perfusion imaging and late gadolinium enhancement imaging. Interference with image quality was assessed by spurious echo imaging and compared to noise levels acquired while operating the electrical parts within the scanner room.
Results
Imaging was performed successfully in all hearts. The system proved suitable for isolated heart perfusion in a novel 3T XMR suite. No significant additional noise was introduced into the scanner room by our set-up.
Conclusions
We have substantially improved a previous version of an isolated perfused pig heart model and made it applicable for MR imaging in a state of the art clinical 3T XMR imaging suite. The use of this system should aid novel CMR sequence development and translation into clinical practice.
doi:10.1556/IMAS.4.2012.4.3
PMCID: PMC3831784  PMID: 24265875
cardiovascular magnetic resonance imaging; coronary artery disease; isolated heart perfusion; Langendorff; pig; translational research
2.  The future of hybrid imaging—part 3: PET/MR, small-animal imaging and beyond 
Insights into imaging  2011;2(3):235-246.
Since the 1990s, hybrid imaging by means of software and hardware image fusion alike allows the intrinsic combination of functional and anatomical image information. This review summarises in three parts the state of the art of dual-technique imaging with a focus on clinical applications. We will attempt to highlight selected areas of potential improvement of combined imaging technologies and new applications. In this third part, we discuss briefly the origins of combined positron emission tomography (PET)/magnetic resonance imaging (MRI). Unlike PET/computed tomography (CT), PET/MRI started out from developments in small-animal imaging technology, and, therefore, we add a section on advances in dual- and multi-modality imaging technology for small animals. Finally, we highlight a number of important aspects beyond technology that should be addressed for a sustained future of hybrid imaging. In short, we predict that, within 10 years, we may see all existing multi-modality imaging systems in clinical routine, including PET/MRI. Despite the current lack of clinical evidence, integrated PET/MRI may become particularly important and clinically useful in improved therapy planning for neurodegenerative diseases and subsequent response assessment, as well as in complementary loco-regional oncology imaging. Although desirable, other combinations of imaging systems, such as single-photon emission computed tomography (SPECT)/MRI may be anticipated, but will first need to go through the process of viable clinical prototyping. In the interim, a combination of PET and ultrasound may become available. As exciting as these new possible triple-technique—imaging systems sound, we need to be aware that they have to be technologically feasible, applicable in clinical routine and cost-effective.
doi:10.1007/s13244-011-0085-4
PMCID: PMC3270262  PMID: 22347950
Hybrid imaging; PET; MRI; PET/MR; Small-animal imaging
3.  The future of hybrid imaging—part 3: PET/MR, small-animal imaging and beyond 
Insights into Imaging  2011;2(3):235-246.
Since the 1990s, hybrid imaging by means of software and hardware image fusion alike allows the intrinsic combination of functional and anatomical image information. This review summarises in three parts the state of the art of dual-technique imaging with a focus on clinical applications. We will attempt to highlight selected areas of potential improvement of combined imaging technologies and new applications. In this third part, we discuss briefly the origins of combined positron emission tomography (PET)/magnetic resonance imaging (MRI). Unlike PET/computed tomography (CT), PET/MRI started out from developments in small-animal imaging technology, and, therefore, we add a section on advances in dual- and multi-modality imaging technology for small animals. Finally, we highlight a number of important aspects beyond technology that should be addressed for a sustained future of hybrid imaging. In short, we predict that, within 10 years, we may see all existing multi-modality imaging systems in clinical routine, including PET/MRI. Despite the current lack of clinical evidence, integrated PET/MRI may become particularly important and clinically useful in improved therapy planning for neurodegenerative diseases and subsequent response assessment, as well as in complementary loco-regional oncology imaging. Although desirable, other combinations of imaging systems, such as single-photon emission computed tomography (SPECT)/MRI may be anticipated, but will first need to go through the process of viable clinical prototyping. In the interim, a combination of PET and ultrasound may become available. As exciting as these new possible triple-technique—imaging systems sound, we need to be aware that they have to be technologically feasible, applicable in clinical routine and cost-effective.
doi:10.1007/s13244-011-0085-4
PMCID: PMC3270262  PMID: 22347950
Hybrid imaging; PET; MRI; PET/MR; Small-animal imaging
4.  Positron Emission Tomography for the Assessment of Myocardial Viability 
Executive Summary
In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.
After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography.
A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed.
The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html
Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis
Magnetic Resonance Imaging for the Assessment of Myocardial Viability: An Evidence-Based Analysis
Objective
The objective of this analysis is to assess the effectiveness and safety of positron emission tomography (PET) imaging using F-18-fluorodeoxyglucose (FDG) for the assessment of myocardial viability. To evaluate the effectiveness of FDG PET viability imaging, the following outcomes are examined:
the diagnostic accuracy of FDG PET for predicting functional recovery;
the impact of PET viability imaging on prognosis (mortality and other patient outcomes); and
the contribution of PET viability imaging to treatment decision making and subsequent patient outcomes.
Clinical Need: Condition and Target Population
Left Ventricular Systolic Dysfunction and Heart Failure
Heart failure is a complex syndrome characterized by the heart’s inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality.
In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD)1 is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997.
Treatment Options
In general, there are three options for the treatment of heart failure: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure.
Myocardial Viability
Left ventricular dysfunction may be permanent if a myocardial scar is formed, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically:
dobutamine echocardiography (echo),
stress echo with contrast,
SPECT using either technetium or thallium,
cardiac magnetic resonance imaging (cardiac MRI), and
positron emission tomography (PET).
Dobutamine Echocardiography
Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 – 10 μg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability.
Stress Echocardiography with Contrast
Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium.
SPECT
SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images.
The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%.
There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%.
Cardiac Magnetic Resonance Imaging
Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. Two types of cardiac MRI are used to assess myocardial viability: dobutamine stress magnetic resonance imaging (DSMR) and delayed contrast-enhanced cardiac MRI (DE-MRI). DE-MRI, the most commonly used technique in Ontario, uses gadolinium-based contrast agents to define the transmural extent of scar, which can be visualized based on the intensity of the image. Hyper-enhanced regions correspond to irreversibly damaged myocardium. As the extent of hyper-enhancement increases, the amount of scar increases, so there is a lower the likelihood of functional recovery.
Cardiac Positron Emission Tomography
Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG).
During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. This collision results in annihilation where the combined mass of the positron and electron is converted into energy in the form of two 511 keV gamma rays, which are then emitted in opposite directions (180 degrees) and captured by an external array of detector elements in the PET gantry. Computer software is then used to convert the radiation emission into images. The system is set up so that it only detects coincident gamma rays that arrive at the detectors within a predefined temporal window, while single photons arriving without a pair or outside the temporal window do not active the detector. This allows for increased spatial and contrast resolution.
Evidence-Based Analysis
Research Questions
What is the diagnostic accuracy of PET for detecting myocardial viability?
What is the prognostic value of PET viability imaging (mortality and other clinical outcomes)?
What is the contribution of PET viability imaging to treatment decision making?
What is the safety of PET viability imaging?
Literature Search
A literature search was performed on July 17, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 to July 16, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. In addition, published systematic reviews and health technology assessments were reviewed for relevant studies published before 2004. Reference lists of included studies were also examined for any additional relevant studies not already identified. The quality of the body of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Inclusion Criteria
Criteria applying to diagnostic accuracy studies, prognosis studies, and physician decision-making studies:
English language full-reports
Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies
Patients with chronic, known CAD
PET imaging using FDG for the purpose of detecting viable myocardium
Criteria applying to diagnostic accuracy studies:
Assessment of functional recovery ≥3 months after revascularization
Raw data available to calculate sensitivity and specificity
Gold standard: prediction of global or regional functional recovery
Criteria applying to prognosis studies:
Mortality studies that compare revascularized patients with non-revascularized patients and patients with viable and non-viable myocardium
Exclusion Criteria
Criteria applying to diagnostic accuracy studies, prognosis studies, and physician decision-making studies:
PET perfusion imaging
< 20 patients
< 18 years of age
Patients with non-ischemic heart disease
Animal or phantom studies
Studies focusing on the technical aspects of PET
Studies conducted exclusively in patients with acute myocardial infarction (MI)
Duplicate publications
Criteria applying to diagnostic accuracy studies
Gold standard other than functional recovery (e.g., PET or cardiac MRI)
Assessment of functional recovery occurs before patients are revascularized
Outcomes of Interest
Diagnostic accuracy studies
Sensitivity and specificity
Positive and negative predictive values (PPV and NPV)
Positive and negative likelihood ratios
Diagnostic accuracy
Adverse events
Prognosis studies
Mortality rate
Functional status
Exercise capacity
Quality of Life
Influence on PET viability imaging on physician decision making
Statistical Methods
Pooled estimates of sensitivity and specificity were calculated using a bivariate, binomial generalized linear mixed model. Statistical significance was defined by P values less than 0.05, where “false discovery rate” adjustments were made for multiple hypothesis testing. Using the bivariate model parameters, summary receiver operating characteristic (sROC) curves were produced. The area under the sROC curve was estimated by numerical integration with a cubic spline (default option). Finally, pooled estimates of mortality rates were calculated using weighted means.
Quality of Evidence
The quality of evidence assigned to individual diagnostic studies was determined using the QUADAS tool, a list of 14 questions that address internal and external validity, bias, and generalizibility of diagnostic accuracy studies. Each question is scored as “yes”, “no”, or “unclear”. The quality of the body of evidence was then assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
A total of 40 studies met the inclusion criteria and were included in this review: one health technology assessment, two systematic reviews, 22 observational diagnostic accuracy studies, and 16 prognosis studies. The available PET viability imaging literature addresses two questions: 1) what is the diagnostic accuracy of PET imaging for the assessment; and 2) what is the prognostic value of PET viability imaging. The diagnostic accuracy studies use regional or global functional recovery as the reference standard to determine the sensitivity and specificity of the technology. While regional functional recovery was most commonly used in the studies, global functional recovery is more important clinically. Due to differences in reporting and thresholds, however, it was not possible to pool global functional recovery.
Functional recovery, however, is a surrogate reference standard for viability and consequently, the diagnostic accuracy results may underestimate the specificity of PET viability imaging. For example, regional functional recovery may take up to a year after revascularization depending on whether it is stunned or hibernating tissue, while many of the studies looked at regional functional recovery 3 to 6 months after revascularization. In addition, viable tissue may not recover function after revascularization due to graft patency or re-stenosis. Both issues may lead to false positives and underestimate specificity. Given these limitations, the prognostic value of PET viability imaging provides the most direct and clinically useful information. This body of literature provides evidence on the comparative effectiveness of revascularization and medical therapy in patients with viable myocardium and patients without viable myocardium. In addition, the literature compares the impact of PET-guided treatment decision making with SPECT-guided or standard care treatment decision making on survival and cardiac events (including cardiac mortality, MI, hospital stays, unintended revascularization, etc).
The main findings from the diagnostic accuracy and prognosis evidence are:
Based on the available very low quality evidence, PET is a useful imaging modality for the detection of viable myocardium. The pooled estimates of sensitivity and specificity for the prediction of regional functional recovery as a surrogate for viable myocardium are 91.5% (95% CI, 88.2% – 94.9%) and 67.8% (95% CI, 55.8% – 79.7%), respectively.
Based the available very low quality of evidence, an indirect comparison of pooled estimates of sensitivity and specificity showed no statistically significant difference in the diagnostic accuracy of PET viability imaging for regional functional recovery using perfusion/metabolism mismatch with FDG PET plus either a PET or SPECT perfusion tracer compared with metabolism imaging with FDG PET alone.
FDG PET + PET perfusion metabolism mismatch: sensitivity, 89.9% (83.5% – 96.4%); specificity, 78.3% (66.3% – 90.2%);
FDG PET + SPECT perfusion metabolism mismatch: sensitivity, 87.2% (78.0% – 96.4%); specificity, 67.1% (48.3% – 85.9%);
FDG PET metabolism: sensitivity, 94.5% (91.0% – 98.0%); specificity, 66.8% (53.2% – 80.3%).
Given these findings, further higher quality studies are required to determine the comparative effectiveness and clinical utility of metabolism and perfusion/metabolism mismatch viability imaging with PET.
Based on very low quality of evidence, patients with viable myocardium who are revascularized have a lower mortality rate than those who are treated with medical therapy. Given the quality of evidence, however, this estimate of effect is uncertain so further higher quality studies in this area should be undertaken to determine the presence and magnitude of the effect.
While revascularization may reduce mortality in patients with viable myocardium, current moderate quality RCT evidence suggests that PET-guided treatment decisions do not result in statistically significant reductions in mortality compared with treatment decisions based on SPECT or standard care protocols. The PARR II trial by Beanlands et al. found a significant reduction in cardiac events (a composite outcome that includes cardiac deaths, MI, or hospital stay for cardiac cause) between the adherence to PET recommendations subgroup and the standard care group (hazard ratio, .62; 95% confidence intervals, 0.42 – 0.93; P = .019); however, this post-hoc sub-group analysis is hypothesis generating and higher quality studies are required to substantiate these findings.
The use of FDG PET plus SPECT to determine perfusion/metabolism mismatch to assess myocardial viability increases the radiation exposure compared with FDG PET imaging alone or FDG PET combined with PET perfusion imaging (total-body effective dose: FDG PET, 7 mSv; FDG PET plus PET perfusion tracer, 7.6 – 7.7 mSV; FDG PET plus SPECT perfusion tracer, 16 – 25 mSv). While the precise risk attributed to this increased exposure is unknown, there is increasing concern regarding lifetime multiple exposures to radiation-based imaging modalities, although the incremental lifetime risk for patients who are older or have a poor prognosis may not be as great as for healthy individuals.
PMCID: PMC3377573  PMID: 23074393
5.  Overlay of conventional angiographic and en-face OCT images enhances their interpretation 
BMC Ophthalmology  2005;5:12.
Background
Combining characteristic morphological and functional information in one image increases pathophysiologic understanding as well as diagnostic accuracy in most clinical settings. En-face optical coherence tomography (OCT) provides a high resolution, transversal OCT image of the macular area combined with a confocal image of the same area (OCT C-scans). Creating an overlay image of a conventional angiographic image onto an OCT image, using the confocal part to facilitate transformation, combines structural and functional information of the retinal area of interest. This paper describes the construction of such overlay images and their aid in improving the interpretation of OCT C-scans.
Methods
In various patients, en-face OCT C-scans (made with a prototype OCT-Ophthalmoscope (OTI, Canada) in use at the Department of Ophthalmology (Academic Medical Centre, Amsterdam, The Netherlands)) and conventional fluorescein angiography (FA) were performed. ImagePro, with a custom made plug-in, was used to make an overlay-image. The confocal part of the OCT C-scan was used to spatially transform the FA image onto the OCT C-scan, using the vascular arcades as a reference. To facilitate visualization the transformed angiographic image and the OCT C-scan were combined in an RGB image.
Results
The confocal part of the OCT C-scan could easily be fused with angiographic images. Overlay showed a direct correspondence between retinal thickening and FA leakage in Birdshot retinochoroiditis, localized the subretinal neovascular membrane and correlated anatomic and vascular leakage features in myopia, and showed the extent of retinal and pigment epithelial detachment in retinal angiomatous proliferation as FA leakage was subject to blocked fluorescence. The overlay mode provided additional insight not readily available in either mode alone.
Conclusion
Combining conventional angiographic images and en-face OCT C-scans assists in the interpretation of both imaging modalities. By combining the physiopathological information in the angiograms with the structural information in the OCT scan, zones of leakage can be correlated to structural changes in the retina or pigment epithelium. This strategy could be used in the evaluation and monitoring of patients with complex central macular pathology.
doi:10.1186/1471-2415-5-12
PMCID: PMC1180453  PMID: 15953392
6.  Magnetic Resonance Imaging (MRI) for the Assessment of Myocardial Viability 
Executive Summary
In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability, an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients undergoing viability assessment. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of noninvasive cardiac imaging modalities.
After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies that can be used for the assessment of myocardial viability: positron emission tomography, cardiac magnetic resonance imaging, dobutamine echocardiography, and dobutamine echocardiography with contrast, and single photon emission computed tomography.
A 2005 review conducted by MAS determined that positron emission tomography was more sensitivity than dobutamine echocardiography and single photon emission tomography and dominated the other imaging modalities from a cost-effective standpoint. However, there was inadequate evidence to compare positron emission tomography and cardiac magnetic resonance imaging. Thus, this report focuses on this comparison only. For both technologies, an economic analysis was also completed.
A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).
The Non-Invasive Cardiac Imaging Technologies for the Assessment of Myocardial Viability is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html
Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis
Magnetic Resonance Imaging for the Assessment of Myocardial Viability: An Evidence-Based Analysis
Objective
The objective of this analysis is to assess the effectiveness and cost-effectiveness of cardiovascular magnetic resonance imaging (cardiac MRI) for the assessment of myocardial viability. To evaluate the effectiveness of cardiac MRI viability imaging, the following outcomes were examined: the diagnostic accuracy in predicting functional recovery and the impact of cardiac MRI viability imaging on prognosis (mortality and other patient outcomes).
Clinical Need: Condition and Target Population
Left Ventricular Systolic Dysfunction and Heart Failure
Heart failure is a complex syndrome characterized by the heart’s inability to maintain adequate blood circulation through the body leading to multiorgan abnormalities and, eventually, death. Patients with heart failure experience poor functional capacity, decreased quality of life, and increased risk of morbidity and mortality.
In 2005, more than 71,000 Canadians died from cardiovascular disease, of which, 54% were due to ischemic heart disease. Left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) 1 is the primary cause of heart failure accounting for more than 70% of cases. The prevalence of heart failure was estimated at one percent of the Canadian population in 1989. Since then, the increase in the older population has undoubtedly resulted in a substantial increase in cases. Heart failure is associated with a poor prognosis: one-year mortality rates were 32.9% and 31.1% for men and women, respectively in Ontario between 1996 and 1997.
Treatment Options
In general, there are three options for the treatment of heart failure: medical treatment, heart transplantation, and revascularization for those with CAD as the underlying cause. Concerning medical treatment, despite recent advances, mortality remains high among treated patients, while, heart transplantation is affected by the limited availability of donor hearts and consequently has long waiting lists. The third option, revascularization, is used to restore the flow of blood to the heart via coronary artery bypass grafting (CABG) or, in some cases, through minimally invasive percutaneous coronary interventions (balloon angioplasty and stenting). Both methods, however, are associated with important perioperative risks including mortality, so it is essential to properly select patients for this procedure.
Myocardial Viability
Left ventricular dysfunction may be permanent, due to the formation of myocardial scar, or it may be reversible after revascularization. Reversible LV dysfunction occurs when the myocardium is viable but dysfunctional (reduced contractility). Since only patients with dysfunctional but viable myocardium benefit from revascularization, the identification and quantification of the extent of myocardial viability is an important part of the work-up of patients with heart failure when determining the most appropriate treatment path. Various non-invasive cardiac imaging modalities can be used to assess patients in whom determination of viability is an important clinical issue, specifically:
dobutamine echocardiography (echo),
stress echo with contrast,
SPECT using either technetium or thallium,
cardiac magnetic resonance imaging (cardiac MRI), and
positron emission tomography (PET).
Dobutamine Echocardiography
Stress echocardiography can be used to detect viable myocardium. During the infusion of low dose dobutamine (5 – 10 µg/kg/min), an improvement of contractility in hypokinetic and akentic segments is indicative of the presence of viable myocardium. Alternatively, a low-high dose dobutamine protocol can be used in which a biphasic response characterized by improved contractile function during the low-dose infusion followed by a deterioration in contractility due to stress induced ischemia during the high dose dobutamine infusion (dobutamine dose up to 40 ug/kg/min) represents viable tissue. Newer techniques including echocardiography using contrast agents, harmonic imaging, and power doppler imaging may help to improve the diagnostic accuracy of echocardiographic assessment of myocardial viability.
Stress Echocardiography with Contrast
Intravenous contrast agents, which are high molecular weight inert gas microbubbles that act like red blood cells in the vascular space, can be used during echocardiography to assess myocardial viability. These agents allow for the assessment of myocardial blood flow (perfusion) and contractile function (as described above), as well as the simultaneous assessment of perfusion to make it possible to distinguish between stunned and hibernating myocardium.
SPECT
SPECT can be performed using thallium-201 (Tl-201), a potassium analogue, or technetium-99 m labelled tracers. When Tl-201 is injected intravenously into a patient, it is taken up by the myocardial cells through regional perfusion, and Tl-201 is retained in the cell due to sodium/potassium ATPase pumps in the myocyte membrane. The stress-redistribution-reinjection protocol involves three sets of images. The first two image sets (taken immediately after stress and then three to four hours after stress) identify perfusion defects that may represent scar tissue or viable tissue that is severely hypoperfused. The third set of images is taken a few minutes after the re-injection of Tl-201 and after the second set of images is completed. These re-injection images identify viable tissue if the defects exhibit significant fill-in (> 10% increase in tracer uptake) on the re-injection images.
The other common Tl-201 viability imaging protocol, rest-redistribution, involves SPECT imaging performed at rest five minutes after Tl-201 is injected and again three to four hours later. Viable tissue is identified if the delayed images exhibit significant fill-in of defects identified in the initial scans (> 10% increase in uptake) or if defects are fixed but the tracer activity is greater than 50%.
There are two technetium-99 m tracers: sestamibi (MIBI) and tetrofosmin. The uptake and retention of these tracers is dependent on regional perfusion and the integrity of cellular membranes. Viability is assessed using one set of images at rest and is defined by segments with tracer activity greater than 50%.
Cardiac Positron Emission Tomography
Positron emission tomography (PET) is a nuclear medicine technique used to image tissues based on the distinct ways in which normal and abnormal tissues metabolize positron-emitting radionuclides. Radionuclides are radioactive analogs of common physiological substrates such as sugars, amino acids, and free fatty acids that are used by the body. The only licensed radionuclide used in PET imaging for viability assessment is F-18 fluorodeoxyglucose (FDG).
During a PET scan, the radionuclides are injected into the body and as they decay, they emit positively charged particles (positrons) that travel several millimetres into tissue and collide with orbiting electrons. This collision results in annihilation where the combined mass of the positron and electron is converted into energy in the form of two 511 keV gamma rays, which are then emitted in opposite directions (180 degrees) and captured by an external array of detector elements in the PET gantry. Computer software is then used to convert the radiation emission into images. The system is set up so that it only detects coincident gamma rays that arrive at the detectors within a predefined temporal window, while single photons arriving without a pair or outside the temporal window do not active the detector. This allows for increased spatial and contrast resolution.
Cardiac Magnetic Resonance Imaging
Cardiac magnetic resonance imaging (cardiac MRI) is a non-invasive, x-ray free technique that uses a powerful magnetic field, radio frequency pulses, and a computer to produce detailed images of the structure and function of the heart. Two types of cardiac MRI are used to assess myocardial viability: dobutamine stress magnetic resonance imaging (DSMR) and delayed contrast-enhanced cardiac MRI (DE-MRI). DE-MRI, the most commonly used technique in Ontario, uses gadolinium-based contrast agents to define the transmural extent of scar, which can be visualized based on the intensity of the image. Hyper-enhanced regions correspond to irreversibly damaged myocardium. As the extent of hyper-enhancement increases, the amount of scar increases, so there is a lower the likelihood of functional recovery.
Evidence-Based Analysis
Research Questions
What is the diagnostic accuracy of cardiac MRI for detecting myocardial viability?
What is the impact of cardiac MRI viability imaging on prognosis (mortality and other clinical outcomes)?
How does cardiac MRI compare with cardiac PET imaging for the assessment of myocardial viability?
What is the contribution of cardiac MRI viability imaging to treatment decision making?
Is cardiac MRI cost-effective compared with other cardiac imaging modalities for the assessment of myocardial viability?
Literature Search
A literature search was performed on October 9, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 until October 9, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria full-text articles were obtained. In addition, published systematic reviews and health technology assessments were reviewed for relevant studies published before 2005. Reference lists were also examined for any additional relevant studies not identified through the search. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Inclusion Criteria
English language full-reports
Published between January 1, 2005 and October 9, 2009
Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies
Patients with chronic, known coronary artery disease (CAD)
Used contrast-enhanced MRI
Assessment of functional recovery ≥ 3 months after revascularization
Exclusion Criteria
< 20 patients
< 18 years of age
Patients with non-ischemic heart disease
Studies conducted exclusively in patients with acute myocardial infarction (MI)
Studies where TP, TN, FP, FN cannot be determined
Outcomes of Interest
Sensitivity
Specificity
Positive predictive value (PPV)
Negative Predictive value (NPV)
Positive likelihood ratio
Negative likelihood ratio
Diagnostic accuracy
Mortality rate (for prognostic studies)
Adverse events
Summary of Findings
Based on the available very low quality evidence, MRI is a useful imaging modality for the detection of viable myocardium. The pooled estimates of sensitivity and specificity for the prediction of regional functional recovery as a surrogate for viable myocardium are 84.5% (95% CI: 77.5% – 91.6%) and 71.0% (95% CI: 68.8% – 79.2%), respectively.
Subgroup analysis demonstrated a statistically significant difference in the sensitivity of MRI to assess myocardial viability for studies using ≤25% hyperenhancement as a viability threshold versus studies using ≤50% hyperenhancement as their viability threshold [78.7 (95% CI: 69.1% - 88.2%) and 96.2 (95% CI: 91.8 – 100.6); p=0.0044 respectively]. Marked differences in specificity were observed [73.6 (95% CI: 62.6% - 84.6%) and 47.2 (95% CI: 22.2 – 72.3); p=0.2384 respectively]; however, these findings were not statistically significant.
There were no statistically significant differences between the sensitivities or specificities for any other subgroups including mean preoperative LVEF, imaging method for function recovery assessment, and length of follow-up.
There was no evidence available to determine whether patients with viable myocardium who are revascularized have a lower mortality rate than those who are treated with medical therapy.
PMCID: PMC3426228  PMID: 23074392
7.  Using corrected Cone-Beam CT image for accelerated partial breast irradiation treatment dose verification: the preliminary experience 
Background
Accurate target localization is mandatory in the accelerated partial breast irradiation (APBI) delivery. Dosimetric verification for positional error will further guarantee the accuracy of treatment delivery. The purpose of this study is to evaluate the clinical feasibility of a cone beam computer tomographic (CBCT) image correction method in APBI.
Methods
A CBCT image correction method was developed. First, rigid image registration was proceeded for CTs and CBCTs; second, these images were separated into four parts; then, ratio images for each of the four parts of planning CTs/CBCTs were calculated and filtered to reduce the high spatial frequency; finally, the enhanced CBCT images were generated combing the four parts. An anthropomorphic thorax rando phantom was used to evaluate the feasibility and accuracy of the CBCT correction method. The CBCT images of consecutive 10 patients receiving APBI were corrected using the above method and dosimetric variations were evaluated. Each set of CBCT is composed of three images: one acquired after skin-marker setup, one after online setup correction and one after treatment delivery.
Results
The phantom study showed the improved accuracy of dose calculation with corrected CBCT. The Dose Volume Histogram (DVH) difference between the planning CT and corrected CBCT is less than the difference between the planning CT and original CBCT. The maximum dose difference between the corrected CBCT and planning CT is 0.8% in PTV_EVAL V100, which is 3.8% between original CBCT and planning. In the patient study, 67.4% of fractions benefit from CBCT setup corrections in PTV_EVAL D95, while in 47.4% of the fractions, reduced dose coverage was found on the post-treatment CBCT. Overall, the CBCT based initial setup correction guaranteed target dose coverage in 9 patients.
Conclusions
A generic CBCT image correction algorithm was created and proved to be easily implemented in clinic. Compared to the original CBCT, the corrected CBCT has more accuracy in dose calculation. The CBCT guided APBI based on initial skin setup is not sufficient to guarantee the accurate dose delivery throughout each fraction. The long treatment delivery time may compromise the target coverage benefits in some patients.
doi:10.1186/1748-717X-8-214
PMCID: PMC3853884  PMID: 24034212
CBCT; APBI; Image correction
8.  Bedside US imaging in multiple trauma patients. Part 1: US findings and techniques 
Journal of Ultrasound  2013;16(4):147-159.
Objectives
The aim of this review article is to present the current views and visions of the role of ultrasound (US) in the management of patients with multiple trauma. The article is divided into two parts. Part 1 (US findings and techniques) will mainly deal with the technical aspects of US imaging in trauma patients and is written also for educational purposes. Part 2 (pathophysiology and US imaging in trauma patients) will deal with integration of US in the clinical and pathophysiological management of multiple trauma patients.
Methods
A non-systematic review of the literature through PubMed search (restricted to the last 10 years) of original articles and review articles.
Results
80 publications were selected for Part 1. Of these 80 articles, the author selected 50 according to personal criteria on the basis of their innovative or original contents (48 original articles and 2 literature review articles); 19 articles were furthermore extracted from the references of the selected publications. The information extracted from these 69 publications was organized into sections dealing with different fields of applications of US imaging in multiple trauma patients.
Conclusions
US imaging in trauma has evolved from the initial use, i.e., early diagnosis of peritoneal effusion (focused abdominal sonography for trauma), to a wider use known as resuscitative ultrasonography, and is today considered as an extension of physical examination to implement a more effective approach to clinical problems and increase the timeliness and safety of interventions.
doi:10.1007/s40477-013-0047-4
PMCID: PMC3846943  PMID: 24432169
Trauma; Ultrasound; Ultrasound findings; Ultrasound technique
9.  Incidental Findings in Imaging Research: Evaluating Incidence, Benefit and Burden 
Archives of internal medicine  2010;170(17):1525-1532.
Context
Little information exists concerning the frequency of clinically significant incidental findings (IFs) identified in the course of imaging research across a broad spectrum of imaging modalities and body regions.
Objective
To estimate the frequency with which research imaging IFs generate further clinical action, and the medical benefit/burden of identifying these IFs.
Design, Setting, and Participants
Retrospective review of subjects undergoing a research imaging exam that was interpreted by a radiologist for IFs in the first quarter of 2004, with 3-year clinical follow-up. An expert panel reviewed IFs generating clinical action to determine medical benefit/burden based on predefined criteria.
Main Outcome Measures
Frequency of (1) IFs that generated further clinical action by modality, body part, age, gender, and (2) IFs resulting in clear medical benefit or burden.
Results
1376 patients underwent 1426 research imaging studies. 40% (567/1426) of exams had at least one IF (1055 total). Risk of an IF increased significantly by age (OR=1.5; [1.4–1.7=95% C.I.] per decade increase). Abdominopelvic CT generated more IFs than other exams (OR=18.9 compared with ultrasound; 9.2% with subsequent clinical action), with CT Thorax and MR brain next (OR=11.9 and 5.9; 2.8% and 2.2% with action, respectively). Overall 6.2% of exams (35/567) with an IF generated clinical action, resulting in clear medical benefit in 1.1% (6/567) and clear medical burden in 0.5% (3/567). In most instances, medical benefit/burden was unclear (4.6%; 26/567).
Conclusions
The frequency of IFs in imaging research exams varies significantly by imaging modality, body region and age. Research imaging studies at high risk for generating IFs can be identified. Routine evaluation of research images by radiologists may result in identification of IFs in a substantial number of cases and subsequent clinical action to address them in much smaller number. Such clinical action can result in medical benefit to a small number of patients.
doi:10.1001/archinternmed.2010.317
PMCID: PMC3721142  PMID: 20876402
10.  Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (IV): Basic principles and parameters for MR imaging within the frame of image based adaptive cervix cancer brachytherapy 
Radiotherapy and Oncology  2012;103(1):113-122.
The GYN GEC-ESTRO working group issued three parts of recommendations and highlighted the pivotal role of MRI for the successful implementation of 3D image-based cervical cancer brachytherapy (BT). The main advantage of MRI as an imaging modality is its superior soft tissue depiction quality. To exploit the full potential of MRI for the better ability of the radiation oncologist to make the appropriate choice for the BT application technique and to accurately define the target volumes and the organs at risk, certain MR imaging criteria have to be fulfilled. Technical requirements, patient preparation, as well as image acquisition protocols have to be tailored to the needs of 3D image-based BT. The present recommendation is focused on the general principles of MR imaging for 3D image-based BT.
Methods and parameters have been developed and progressively validated from clinical experience from different institutions (IGR, Universities of Vienna, Leuven, Aarhus and Ljubljana) and successfully applied during expert meetings, contouring workshops, as well as within clinical and interobserver studies.
It is useful to perform pelvic MRI scanning prior to radiotherapy (“Pre-RT-MRI examination”) and at the time of BT (“BT MRI examination”) with one MR imager. Both low and high-field imagers, as well as both open and close magnet configurations conform to the requirements of 3D image-based cervical cancer BT. Multiplanar (transversal, sagittal, coronal and oblique image orientation) T2-weighted images obtained with pelvic surface coils are considered as the golden standard for visualisation of the tumour and the critical organs. The use of complementary MRI sequences (e.g. contrast-enhanced T1-weighted or 3D isotropic MRI sequences) is optional. Patient preparation has to be adapted to the needs of BT intervention and MR imaging. It is recommended to visualise and interpret the MR images on dedicated DICOM-viewer workstations, which should also assist the contouring procedure. Choice of imaging parameters and BT equipment is made after taking into account aspects of interaction between imaging and applicator reconstruction, as well as those between imaging, geometry and dose calculation.
In a prospective clinical context, to implement 3D image-based cervical cancer brachytherapy and to take advantage of its full potential, it is essential to successfully meet the MR imaging criteria described in the present recommendations of the GYN GEC-ESTRO working group.
doi:10.1016/j.radonc.2011.12.024
PMCID: PMC3336085  PMID: 22296748
Recommendations; MRI; Image based adaptive cervix cancer brachytherapy
11.  Building a medical multimedia database system to integrate clinical information: an application of high-performance computing and communications technology. 
The rapid growth of diagnostic-imaging technologies over the past two decades has dramatically increased the amount of nontextual data generated in clinical medicine. The architecture of traditional, text-oriented, clinical information systems has made the integration of digitized clinical images with the patient record problematic. Systems for the classification, retrieval, and integration of clinical images are in their infancy. Recent advances in high-performance computing, imaging, and networking technology now make it technologically and economically feasible to develop an integrated, multimedia, electronic patient record. As part of The National Library of Medicine's Biomedical Applications of High-Performance Computing and Communications program, we plan to develop Image Engine, a prototype microcomputer-based system for the storage, retrieval, integration, and sharing of a wide range of clinically important digital images. Images stored in the Image Engine database will be indexed and organized using the Unified Medical Language System Metathesaurus and will be dynamically linked to data in a text-based, clinical information system. We will evaluate Image Engine by initially implementing it in three clinical domains (oncology, gastroenterology, and clinical pathology) at the University of Pittsburgh Medical Center.
Images
PMCID: PMC225998  PMID: 7703940
12.  The Role of Abcb5 Alleles in Susceptibility to Haloperidol-Induced Toxicity in Mice and Humans 
PLoS Medicine  2015;12(2):e1001782.
Background
We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study.
Methods and Findings
A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered.
Conclusions
ABCB5 alleles alter susceptibility to HIT in mouse and humans. This discovery leads to a new model that (at least in part) explains inter-individual differences in susceptibility to a drug-induced CNS toxicity.
Gary Peltz and colleagues examine the role of ABCB5 alleles in haloperidol-induced toxicity in a murine genetic model and humans treated with haloperidol.
Editors' Summary
Background
The brain is the control center of the human body. This complex organ controls thoughts, memory, speech, and movement, it is the seat of intelligence, and it regulates the function of many organs. The brain comprises many different parts, all of which work together but all of which have their own special functions. For example, the forebrain is involved in intellectual activities such as thinking whereas the hindbrain controls the body’s vital functions and movements. Messages are passed between the various regions of the brain and to other parts of the body by specialized cells called neurons, which release and receive signal molecules known as neurotransmitters. Like all the organs in the body, blood vessels supply the brain with the oxygen, water, and nutrients it needs to function. Importantly, however, the brain is protected from infectious agents and other potentially dangerous substances circulating in the blood by the “blood-brain barrier,” a highly selective permeability barrier that is formed by the cells lining the fine blood vessels (capillaries) within the brain.
Why Was This Study Done?
Although drugs have been developed to treat various brain disorders, more active and less toxic drugs are needed to improve the treatment of many if not most of these conditions. Unfortunately, relatively little is known about how the blood-brain barrier regulates the entry of drugs into the brain or about the genetic factors that affect the brain’s susceptibility to drug-induced toxicities. It is not known, for example, why about half of patients given haloperidol—a drug used to treat psychotic disorders (conditions that affect how people think, feel, or behave)—develop tremors and other symptoms caused by alterations in the brain region that controls voluntary movements. Here, to improve our understanding of how drugs enter the brain and impact its function, the researchers investigate the genetic factors that affect haloperidol-induced toxicity by genetically analyzing several inbred mouse strains (every individual in an inbred mouse strain is genetically identical) with different susceptibilities to haloperidol-induced toxicity and by undertaking a human genetic association study (a study that looks for non-chance associations between specific traits and genetic variants).
What Did the Researchers Do and Find?
The researchers used a database of genetic variants called single nucleotide polymorphisms (SNPs) and a computational genetic mapping approach to show first that variations within the gene encoding Abcb5 affected susceptibility to haloperidol-induced toxicity (indicated by changes in the length of time taken by mice to move their paws when placed on an inclined wire-mesh screen) among inbred mouse strains. Abcb5 is an ATP-binding cassette transporter, a type of protein that moves molecules across cell membranes. The researchers next showed that Abcb5 is expressed in brain capillaries, which is the location of the blood-brain barrier. Abcb5 was also expressed in cerebellar Purkinje cells, which help to control motor (intentional) movements. They also measured the measured the effect of haloperidol and the haloperidol concentration in brain tissue sections in mice that were genetically engineered to make no Abcb5 (Abcb5 knockout mice). Finally, the researchers investigated whether specific alleles (alternative versions) of ABCB5 are associated with haloperidol-induced toxicity in people. Among a group of 85 patients treated with haloperidol for a psychotic illness, one specific ABCB5 allele was associated with haloperidol-induced toxicity during the first few days of treatment.
What Do These Findings Mean?
These findings indicate that Abcb5 is a component of the blood-brain barrier in mice and suggest that genetic variants in the gene encoding this protein underlie, at least in part, the differences in susceptibility to haloperidol-induced toxicity seen among inbred mice strains. Moreover, the human genetic association study indicates that a specific ABCB5 allele also affects the susceptibility of people to haloperidol-induced toxicity. The researchers note that other ABCB5 alleles or other genetic factors that affect haloperidol-induced toxicity in people might emerge if larger groups of patients were studied. However, based on their findings, the researchers propose a new model for the genetic mechanisms that underlie inter-individual and cell type-specific differences in susceptibility to haloperidol-induced brain toxicity. If confirmed in future studies, this model might facilitate the development of more effective and less toxic drugs to treat a range of brain disorders.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001782.
The US National Institute of Neurological Disorders and Stroke provides information about a wide range of brain diseases (in English and Spanish); its fact sheet “Brain Basics: Know Your Brain” is a simple introduction to the human brain; its “Blueprint Neurotherapeutics Network” was established to develop new drugs for disorders affecting the brain and other parts of the nervous system
MedlinePlus provides links to additional resources about brain diseases and their treatment (in English and Spanish)
Wikipedia provides information about haloperidol, about ATP-binding cassette transporters and about genetic association (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001782
PMCID: PMC4315575  PMID: 25647612
13.  Preclinical Whole-body Fluorescence Imaging: Review of Instruments, Methods and Applications 
Fluorescence sampling of cellular function is widely used in all aspects of biology, allowing the visualization of cellular and sub-cellular biological processes with spatial resolutions in the range from nanometers up to centimeters. Imaging of fluorescence in vivo has become the most commonly used radiological tool in all pre-clinical work. In the last decade, full-body pre-clinical imaging systems have emerged with a wide range of utilities and niche application areas. The range of fluorescent probes that can be excited in the visible to near-infrared part of the electromagnetic spectrum continues to expand, with the most value for in vivo use being beyond the 630 nm wavelength, because the absorption of light sharply decreases. Whole-body in vivo fluorescence imaging has not yet reached a state of maturity that allows its routine use in the scope of large-scale pre-clinical studies. This is in part due to an incomplete understanding of what the actual fundamental capabilities and limitations of this imaging modality are. However, progress is continuously being made in research laboratories pushing the limits of the approach to consistently improve its performance in terms of spatial resolution, sensitivity and quantification. This paper reviews this imaging technology with a particular emphasis on its potential uses and limitations, the required instrumentation, and the possible imaging geometries and applications. A detailed account of the main commercially available systems is provided as well as some perspective relating to the future of the technology development. Although the vast majority of applications of in vivo small animal imaging are based on epi-illumination planar imaging, the future success of the method relies heavily on the design of novel imaging systems based on state-of-the-art optical technology used in conjunction with high spatial resolution structural modalities such as MRI, CT or ultra-sound.
doi:10.1016/j.jphotobiol.2009.11.007
PMCID: PMC3678966  PMID: 20031443
fluorescence; imaging; tomography; commercial; molecular; fluorophore; small animal; diagnostic
14.  Computerized tongue image segmentation via the double geo-vector flow 
Chinese Medicine  2014;9:7.
Background
Visual inspection for tongue analysis is a diagnostic method in traditional Chinese medicine (TCM). Owing to the variations in tongue features, such as color, texture, coating, and shape, it is difficult to precisely extract the tongue region in images. This study aims to quantitatively evaluate tongue diagnosis via automatic tongue segmentation.
Methods
Experiments were conducted using a clinical image dataset provided by the Laboratory of Traditional Medical Syndromes, Shanghai University of TCM. First, a clinical tongue image was refined by a saliency window. Second, we initialized the tongue area as the upper binary part and lower level set matrix. Third, a double geo-vector flow (DGF) was proposed to detect the tongue edge and segment the tongue region in the image, such that the geodesic flow was evaluated in the lower part, and the geo-gradient vector flow was evaluated in the upper part.
Results
The performance of the DGF was evaluated using 100 images. The DGF exhibited better results compared with other representative studies, with its true-positive volume fraction reaching 98.5%, its false-positive volume fraction being 1.51%, and its false-negative volume fraction being 1.42%. The errors between the proposed automatic segmentation results and manual contours were 0.29 and 1.43% in terms of the standard boundary error metrics of Hausdorff distance and mean distance, respectively.
Conclusions
By analyzing the time complexity of the DGF and evaluating its performance via standard boundary and area error metrics, we have shown both efficiency and effectiveness of the DGF for automatic tongue image segmentation.
doi:10.1186/1749-8546-9-7
PMCID: PMC3922256  PMID: 24507094
15.  Role of magnetic resonance diffusion imaging and apparent diffusion coefficient values in the evaluation of spinal tuberculosis in Indian patients 
Aim:
To define a range of apparent diffusion coefficient values in spinal tuberculosis and to evaluate the sensitivity of diffusion-weighted magnetic resonance imaging (DW-MRI) and apparent diffusion coefficient values in patients of spinal tuberculosis.
Materials and Methods:
This study was conducted over a period of 20 months and included 110 patients with a total of 230 vertebral bodies. The study was performed in two parts. The first part included all patients of known tuberculosis and patients with classical features of tuberculosis. The second part included patients with spinal pathology of indeterminate etiology. All the patients underwent a routine MRI examination along with diffusion sequences. The apparent diffusion coefficient (ADC) values were calculated from all the involved vertebral bodies.
Results:
The mean ADC value of affected vertebrae in first part of the study was found to be 1.4 ± 0.20 × 10−3 mm2/s. This ADC value was then applied to patients in the second part of study in order to determine its ability in predicting tuberculosis. This range of ADC values was significantly different from the mean ADC values of normal vertebrae and those with metastatic involvement. However, there was an overlap of ADC values in a few tuberculous vertebrae with the ADC values in metastatic vertebrae.
Conclusion:
We found that DW-MRI and ADC values may help in the differentiation of spinal tuberculosis from other lesions of similar appearance. However, an overlap of ADC values was noted with those of metastatic vertebrae. Therefore diffusion imaging and ADC values must always be interpreted in association with clinical history and routine MRI findings and not in isolation.
doi:10.4103/0971-3026.73544
PMCID: PMC3056625  PMID: 21423903
Diffusion MRI; spine; tuberculosis
16.  Diagnosis and treatment of craniocervical dissociation in 48 consecutive survivors  
Study type: Case series
Introduction: Craniocervical dissociation (CCD) is an uncommon and frequently fatal injury with few reports in the literature of survivors. Advances in automobile safety and improved emergency medical services have resulted in increased survival. Timely diagnosis and treatment are imperative for optimal outcome. Regrettably, the presence of multiple life threatening injuries, low clinical suspicion, and lack of familiarity with the upper cervical radiographic anatomy frequently lead to missed or delayed diagnosis.
Objective: This paper represents the largest series of surgically treated CCD survivors. The goal of this study is to determine if any improvements have been made in the timely diagnosis of CCD while performing a complete patient evaluation.
Methods: Following institutional review board approval, a search of the Harborview Medical Center (HMC) trauma registry was conducted for all surgically treated CCD patients between 1996 and 2008. Forty-eight consecutive cases were identified. A retrospective review of the radiological and clinical results with emphasis on timing of diagnosis, modality used for diagnosis (Figures 1 and 2), clinical effect of delayed diagnosis, potential clinical or imaging warning signs, and response to treatment was performed. Thirty-one patients treated from 2003 to 2008 were compared to 17 patients that were treated from 1996 to 2002 and reported previously.1
Initial lateral C-spine radiograph obtained as part of the initial ATLS survey demonstrating an occiput C1 distractive injury.
Sagittal C-spine CT scan obtained as part of the initial ATLS survey demonstrating an occiput C2 distractive injury.
All patients sustained high-energy injuries and were evaluated according to standard Advanced Trauma Life Support (ATLS) protocols. Once CCD was identified or suspected, provisional stabilization was applied and MRI evaluation performed (Figure 3). Definitive surgical management with rigid posterior instrumentation and fusion was performed as soon as physiologically possible (Figures 4 and 5).
Preoperative coronal T2 MRI sequences demonstrating increased signal intensity on the occiput-C1 and C1-2 joints.
Postoperative lateral C-spine x-ray showing rigid posterior instrumented fusion from occiput to C2.
Postoperative sagittal C-spine x-ray showing rigid posterior instrumented fusion from occiput to C2.
Results: Craniocervical dissociation was identified on initial cervical spine imaging in 26 patients (84%). The remaining five patients (16%) were diagnosed by cervical spine MRI. Twenty-three patients (74.2%) were diagnosed within 24 hours of presentation, four (22.6%) were diagnosed between 24 and 48 hours, and one (3.2%) experienced a delay of greater than 48 hours (Table 1). In comparison, four (24%) of the previously treated 17 patients were diagnosed on initial cervical spine imaging. Four patients (24%) were diagnosed within 24 hours of presentation, nine (52%) were diagnosed between 24 and 48 hours, and four (24%) experienced a delay of greater than 48 hours.
There were no cases of craniocervical pseudarthrosis or hardware failure during a mean nine-month follow-up period. Four patients expired during their hospital course. The mean American Spinal Injury Association (ASIA) motor score of 47 improved to 60, and the number of patients with useful motor function (ASIA Grade D or E) increased from eight (26%) preoperatively to 17 (55%) postoperatively.
Conclusions: Improvements have been made in time to diagnosis of CCD in recent years. Increased awareness and the routine use of CT scan as part of the initial ATLS evaluation account for this progress. Expedited diagnosis has decreased preoperative neurological deterioration. However, differences in length of follow-up between the two groups preclude conclusions about its effect on long-term neurological outcome.
doi:10.1055/s-0028-1100920
PMCID: PMC3623094  PMID: 23637673
17.  Indications for computed tomography (CT-) diagnostics in proximal humeral fractures: a comparative study of plain radiography and computed tomography 
Background
Precise indications for computed tomography (CT) in proximal humeral fractures are not established. The purpose of this study was a comparison of conventional radiographic views with different CT reconstructions with 2 D and 3 D imaging to establish indications for additional CT diagnostics depending on the fractured parts.
Methods
In a prospective diagnostic study in two level 1 trauma centers, 44 patients with proximal humeral fractures were diagnosed with conventional X-rays (22 AP + axillary views, 22 AP + scapular Y-views) and CT (multi-planar reconstruction (MPR) and maximum intensity projection (MIP)) with 2 D and 3 D imaging. 3 observers assessed the technical image quality, the assessment of the relevant anatomical structures (2-sample-t-test) and the percentage of the osseous overlap of the proximal humerus (Welch-test) using a scoring system. The quality of the different diagnostic methods was assessed according to the number of fractured parts (Bonferroni-Holm adjustment).
Results
There was significantly more overlap of the fractured region on the scapular Y-views (mean 71.5%, range 45–90%) than on axillary views (mean 56.2%, range 10.5–100%). CT-diagnostics allowed a significantly better assessment of the relevant structures than conventional diagnostics (p < 0.05) independently of the fracture severity (two-, three-, and four-part fractures).
Conclusion
Conventional X-rays with AP view and a high-quality axillary view are useful for primary diagnostics of the fracture and often but not always show a clear presentation of the relevant bony structures such as both tuberosities, the glenoid and humeral head. CT with thin slices technology and additional 3 D imaging provides always a clear presentation of the fractured region. Clinically, a CT should be performed – independently of the number of fractured parts – when the proximal humerus and the shoulder joint are not presented with sufficient X-ray-quality to establish a treatment plan.
doi:10.1186/1471-2474-10-33
PMCID: PMC2678973  PMID: 19341472
18.  The future of hybrid imaging—part 2: PET/CT 
Insights into Imaging  2011;2(3):225-234.
Since the 1990s, hybrid imaging by means of software and hardware image fusion alike allows the intrinsic combination of functional and anatomical image information. This review summarises the state-of-the-art of dual-modality imaging with a focus on clinical applications. We highlight selected areas for potential improvement of combined imaging technologies and new applications. In the second part, we briefly review the background of dual-modality PET/CT imaging, discuss its main applications and attempt to predict technological and methodological improvements of combined PET/CT imaging. After a decade of clinical evaluation, PET/CT will continue to have a significant impact on patient management, mainly in the area of oncological diseases. By adopting more innovative acquisition schemes and data processing PET/CT will become a fast and dose-efficient imaging method and an integral part of state-of-the-art clinical patient management.
doi:10.1007/s13244-011-0069-4
PMCID: PMC3288992  PMID: 23099865
Hybrid imaging; PET; CT; PET/CT
19.  Heterotopic ossification of the knee joint in intensive care unit patients: early diagnosis with magnetic resonance imaging 
Critical Care  2006;10(5):R152.
Introduction
Heterotopic ossification (HO) is the formation of bone in soft tissues. The purpose of the present study was to evaluate the magnetic resonance imaging (MRI) findings on clinical suspicion of HO in the knee joint of patients hospitalised in the intensive care unit (ICU).
Methods
This was a case series of 11 patients requiring prolonged ventilation in the ICU who had the following diagnoses: head trauma (nine), necrotising pancreatitis (one), and fat embolism (one). On clinical suspicion of HO, x-rays and MRI of the knee joint were performed. Follow-up x-rays and MRI were also performed.
Results
First x-rays were negative, whereas MRI (20.2 ± 6.6 days after admission) showed joint effusion and in fast spin-echo short time inversion-recovery (STIR) images a 'lacy pattern' of the muscles vastus lateralis and medialis. The innermost part of the vastus medialis exhibited homogeneous high signal. Contrast-enhanced fat-suppressed T1-weighted images also showed a 'lacy pattern.' On follow-up (41.4 ± 6.6 days after admission), STIR and contrast-enhanced T1-weighted images depicted heterogeneous high signal and heterogeneous enhancement, respectively, at the innermost part of the vastus medialis, whereas x-rays revealed a calcified mass in the same position. Overall, positive MRI findings appeared simultaneously with clinical signs (1.4 ± 1.2 days following clinical diagnosis) whereas x-ray diagnosis was evident at 23 ± 4.3 days (p = 0.002).
Conclusion
MRI of the knee performed on clinical suspicion shows a distinct imaging pattern confirming the diagnosis of HO earlier than other methods. MRI diagnosis may have implications for early intervention in the development of HO.
doi:10.1186/cc5083
PMCID: PMC1751061  PMID: 17074077
20.  Magnetic Resonance Imaging Research in Sub-Saharan Africa: Challenges and Satellite-Based Networking Implementation 
As part of an NIH-funded study of malaria pathogenesis, a magnetic resonance (MR) imaging research facility was established in Blantyre, Malaŵi to enhance the clinical characterization of pediatric patients with cerebral malaria through application of neurological MR methods. The research program requires daily transmission of MR studies to Michigan State University (MSU) for clinical research interpretation and quantitative post-processing. An intercontinental satellite-based network was implemented for transmission of MR image data in Digital Imaging and Communications in Medicine (DICOM) format, research data collection, project communications, and remote systems administration. Satellite Internet service costs limited the bandwidth to symmetrical 384 kbit/s. DICOM routers deployed at both the Malaŵi MRI facility and MSU manage the end-to-end encrypted compressed data transmission. Network performance between DICOM routers was measured while transmitting both mixed clinical MR studies and synthetic studies. Effective network latency averaged 715 ms. Within a mix of clinical MR studies, the average transmission time for a 256 × 256 image was ~2.25 and ~6.25 s for a 512 × 512 image. Using synthetic studies of 1,000 duplicate images, the interquartile range for 256 × 256 images was [2.30, 2.36] s and [5.94, 6.05] s for 512 × 512 images. Transmission of clinical MRI studies between the DICOM routers averaged 9.35 images per minute, representing an effective channel utilization of ~137% of the 384-kbit/s satellite service as computed using uncompressed image file sizes (including the effects of image compression, protocol overhead, channel latency, etc.). Power unreliability was the primary cause of interrupted operations in the first year, including an outage exceeding 10 days.
doi:10.1007/s10278-010-9323-4
PMCID: PMC3033988  PMID: 20714916
Magnetic resonance imaging; computer networks; image distribution; wide area network (WAN); brain imaging; satellite-based networks; sub-Saharan Africa; DICOM router
21.  Magnetic Resonance Imaging Research in Sub-Saharan Africa: Challenges and Satellite-Based Networking Implementation 
Journal of Digital Imaging  2010;24(4):729-738.
As part of an NIH-funded study of malaria pathogenesis, a magnetic resonance (MR) imaging research facility was established in Blantyre, Malaŵi to enhance the clinical characterization of pediatric patients with cerebral malaria through application of neurological MR methods. The research program requires daily transmission of MR studies to Michigan State University (MSU) for clinical research interpretation and quantitative post-processing. An intercontinental satellite-based network was implemented for transmission of MR image data in Digital Imaging and Communications in Medicine (DICOM) format, research data collection, project communications, and remote systems administration. Satellite Internet service costs limited the bandwidth to symmetrical 384 kbit/s. DICOM routers deployed at both the Malaŵi MRI facility and MSU manage the end-to-end encrypted compressed data transmission. Network performance between DICOM routers was measured while transmitting both mixed clinical MR studies and synthetic studies. Effective network latency averaged 715 ms. Within a mix of clinical MR studies, the average transmission time for a 256 × 256 image was ~2.25 and ~6.25 s for a 512 × 512 image. Using synthetic studies of 1,000 duplicate images, the interquartile range for 256 × 256 images was [2.30, 2.36] s and [5.94, 6.05] s for 512 × 512 images. Transmission of clinical MRI studies between the DICOM routers averaged 9.35 images per minute, representing an effective channel utilization of ~137% of the 384-kbit/s satellite service as computed using uncompressed image file sizes (including the effects of image compression, protocol overhead, channel latency, etc.). Power unreliability was the primary cause of interrupted operations in the first year, including an outage exceeding 10 days.
doi:10.1007/s10278-010-9323-4
PMCID: PMC3033988  PMID: 20714916
Magnetic resonance imaging; computer networks; image distribution; wide area network (WAN); brain imaging; satellite-based networks; sub-Saharan Africa; DICOM router
22.  SPIRS: A Web-based Image Retrieval System for Large Biomedical Databases 
Purpose
With the increasing use of images in disease research, education, and clinical medicine, the need for methods that effectively archive, query, and retrieve these images by their content is underscored. This paper describes the implementation of a Web-based retrieval system called SPIRS (Spine Pathology & Image Retrieval System), which permits exploration of a large biomedical database of digitized spine x-ray images and data from a national health survey using a combination of visual and textual queries.
Methods
SPIRS is a generalizable framework that consists of four components: a client applet, a gateway, an indexing and retrieval system, and a database of images and associated text data. The prototype system is demonstrated using text and imaging data collected as part of the second U.S. National Health and Nutrition Examination Survey (NHANES II). Users search the image data by providing a sketch of the vertebral outline or selecting an example vertebral image and some relevant text parameters. Pertinent pathology on the image/sketch can be annotated and weighted to indicate importance.
Results
During the course of development, we explored different algorithms to perform functions such as segmentation, indexing, and retrieval. Each algorithm was tested individually and then implemented as part of SPIRS. To evaluate the overall system, we first tested the system’s ability to return similar vertebral shapes from the database given a query shape. Initial evaluations using visual queries only (no text) have shown that the system achieves up to 68% accuracy in finding images in the database that exhibit similar abnormality type and severity. Relevance feedback mechanisms have been shown to increase accuracy by an additional 22% after three iterations. While we primarily demonstrate this system in the context of retrieving vertebral shape, our framework has also been adapted to search a collection of 100,000 uterine cervix images to study the progression of cervical cancer.
Conclusions
SPIRS is automated, easily accessible, and integratable with other complementary information retrieval systems. The system supports the ability for users to intuitively query large amounts of imaging data by providing visual examples and text keywords and has beneficial implications in the areas of research, education, and patient care.
doi:10.1016/j.ijmedinf.2008.09.006
PMCID: PMC2693318  PMID: 18996737
Medical informatics applications; Information storage and retrieval; Content-based image retrieval; Visual access methods; Web-based systems
23.  Assessment of Bone Quality and Structure 
According to an NIH Consensus Conference in 2001, bone quality is related to various aspects of bone: its micro- and macroarchitecture, turnover, resorption and mineralisation. Radiological imaging techniques can be used to visualise and quantify bone micro- and macroarchitecture in vivo.
Macroarchitecture
The parameters of bone macrostructure can be obtained using various methods: X-rays, DXA, QUS, QCT and MR imaging.
The parameters derived from traditional radiological investigations (such as hip axis length, neck width and neck shaft angle), like Singh indices, have been shown to be of limited usefulness in the diagnosis of osteoporosis and, indeed, have never been accepted as standard diagnostic tools.
Geometrical parameters (e.g. hip axis length, length and width of the neck of the femur) have also been obtained from DXA images of the hip; it has been shown that an increase, of two standard deviations, in hip axis length triples the risk of hip fracture. These measures have been used in numerous studies, but none has been shown, convincingly, to add substantial information to BMD in predicting status or fracture risk.
QUS provides quantitative parameters that are used to establish the properties of bone tissue. This method offers a series of advantages: smaller dimensions, simple and rapid measurements, no need for ionising radiations, as well as low cost compared with DXA and QCT. Consequently, the QUS seems to generate more information on bone fragility, to the extent that, at present, QUS systems are the ones most used in osteoporotic fracture risk prediction. Given the availability of various techniques for evaluating risk fracture, the T-score approach to fracture risk assessment seems to present some shortcomings linked to discrepancies between examined sites and techniques used. Ten-year fracture probability is the best method for determining the threshold for intervention.
QCT images, too, have been used to measure geometrical parameters; it was found that patients with osteoporotic fractures had a greater vertebral axial cross-section than fracture-free patients, and that treatment with parathormone increases the vertebral area. Initial studies have been performed using MRI data to generate geometrical parameters.
Microarchitecture
The microarchitectural parameters of trabecular bone structure have proved to be more useful than bone macroarchitecture measurements in evaluation of bone quality and in distinguishing between patients with and without osteoporotic fractures. Clinical studies have been performed using high-resolution techniques to study trabecular bone architecture; these techniques include multidetector CT, magnetic resonance and in vivo micro-CT. Indeed, using multidetector CT, bone structure measurements were shown to be better than BMD in differentiating between the two patient groups. However, the radiation dose needed to obtain sufficiently high quality images was found to be necessarily rather high, which is thus a potential limitation of this technique. HR-MR imaging, on the other hand, does not involve the use of radiation and is therefore more attractive for scientific studies. It has been used to study trabecular bone architecture in a number of studies, showing a good ability to discriminate between patients with and without osteoporotic fractures. The sites most frequently studied using HR-MR imaging are the distal radius and heel. The disadvantage of MR-based techniques is that the use of standard 1.5 Tesla systems is limited to peripheral parts, like the heel, distal tibia and distal radius, whereas higher magnetic fields (3 Tesla) would allow better visualisation of the trabecular bone structure and examination of more central parts of the skeleton, such as the proximal femur.
In vivo micro-CT is a recently developed imaging technique; initial studies on its ability to quantify the bone microarchitecture of the peripheral skeleton have given good results in terms of reproducibility and also capacity to detect age- and disease-related changes.
In conclusion, in vivo imaging of bone macro- and microarchitecture is possible, and a certain number of studies, geared at the optimisation and clinical application of these techniques, have already been conducted. The NIH in the USA are promoting and supporting the concept of bone quality, which in the future could lead to new diagnostic standards and techniques for analysing bone structure and will probably change the definition of osteoporosis.
PMCID: PMC3213808
24.  Cardiac Magnetic Resonance Imaging for the Diagnosis of Coronary Artery Disease 
Executive Summary
In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.
After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).
The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html
Single Photon Emission Computed Tomography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Stress Echocardiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Stress Echocardiography with Contrast for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Cardiac Magnetic Resonance Imaging for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Pease note that two related evidence-based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website:
Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis
Magnetic Resonance Imaging for the Assessment of Myocardial Viability: an Evidence-Based Analysis
The Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled:
The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [Internet]. Available from: http://theta.utoronto.ca/reports/?id=7
Objective
The objective of this analysis was to determine the diagnostic accuracy of cardiac magnetic resonance imaging (MRI) for the diagnosis of patients with known/suspected coronary artery disease (CAD) compared to coronary angiography.
Cardiac MRI
Stress cardiac MRI is a non-invasive, x-ray free imaging technique that takes approximately 30 to 45 minutes to complete and can be performed using to two different methods, a) perfusion imaging following a first pass of an intravenous bolus of gadolinium contrast, or b) wall motion imaging. Stress is induced pharmacologically with either dobutamine, dipyridamole, or adenosine, as physical exercise is difficult to perform within the magnet bore and often induces motion artifacts. Alternatives to stress cardiac perfusion MRI include stress single-photon emission computed tomography (SPECT) and stress echocardiography (ECHO). The advantage of cardiac MRI is that it does not pose the radiation burden associated with SPECT. During the same sitting, cardiac MRI can also assess left and right ventricular dimensions, viability, and cardiac mass. It may also mitigate the need for invasive diagnostic coronary angiography in patients with intermediate risk factors for CAD.
Evidence-Based Analysis
Literature Search
A literature search was performed on October 9, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2005 to October 9, 2008. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Given the large amount of clinical heterogeneity of the articles meeting the inclusion criteria, as well as suggestions from an Expert Advisory Panel Meeting held on October 5, 2009, the inclusion criteria were revised to examine the effectiveness of cardiac MRI for the detection of CAD.
Heath technology assessments, systematic reviews, randomized controlled trials, observational studies
≥20 adult patients enrolled.
Published 2004-2009
Licensed by Health Canada
For diagnosis of CAD:
Reference standard is coronary angiography
Significant CAD defined as ≥ 50% coronary stenosis
Patients with suspected or known CAD
Reported results by patient, not segment
Non-English studies
Grey literature
Planar imaging
MUGA
Patients with recent MI (i.e., within 1 month)
Patients with non-ischemic heart disease
Studies done exclusively in special populations (e.g., women, diabetics)
Outcomes of Interest
Sensitivity and specificity
Area under the curve (AUC)
Diagnostic odds ratio (DOR)
Summary of Findings
Stress cardiac MRI using perfusion analysis yielded a pooled sensitivity of 0.91 (95% CI: 0.89 to 0.92) and specificity of 0.79 (95% CI: 0.76 to 0.82) for the detection of CAD.
Stress cardiac MRI using wall motion analysis yielded a pooled sensitivity of 0.81 (95% CI: 0.77 to 0.84) and specificity of 0.85 (95% CI: 0.81 to 0.89) for the detection of CAD.
Based on DORs, there was no significant difference between pooled stress cardiac MRI using perfusion analysis and pooled stress cardiac MRI using wall motion analysis (P=0.26) for the detection of CAD.
Pooled subgroup analysis of stress cardiac MRI using perfusion analysis showed no significant difference in the DORs between 1.5T and 3T MRI (P=0.72) for the detection of CAD.
One study (N=60) was identified that examined stress cardiac MRI using wall motion analysis with a 3T MRI. The sensitivity and specificity of 3T MRI were 0.64 (95% CI: 0.44 to 0.81) and 1.00 (95% CI: 0.89 to 1.00), respectively, for the detection of CAD.
The effectiveness of stress cardiac MRI for the detection of CAD in unstable patients with acute coronary syndrome was reported in only one study (N=35). Using perfusion analysis, the sensitivity and specificity were 0.72 (95% CI: 0.53 to 0.87) and 1.00 (95% CI: 0.54 to 1.00), respectively, for the detection of CAD.
Ontario Health System Impact Analysis
According to an expert consultant, in Ontario:
Stress first pass perfusion is currently performed in small numbers in London (London Health Sciences Centre) and Toronto (University Health Network at the Toronto General Hospital site and Sunnybrook Health Sciences Centre).
Stress wall motion is only performed as part of research protocols and not very often.
Cardiac MRI machines use 1.5T almost exclusively, with 3T used in research for first pass perfusion.
On November 25 2009, the Cardiac Imaging Expert Advisory Panel met and made the following comments about stress cardiac MRI for perfusion analysis:
Accessibility to cardiac MRI is limited and generally used to assess structural abnormalities. Most MRIs in Ontario are already in 24–hour, constant use and it would thus be difficult to add cardiac MRI for CAD diagnosis as an additional indication.
The performance of cardiac MRI for the diagnosis of CAD can be technically challenging.
GRADE Quality of Evidence for Cardiac MRI in the Diagnosis of CAD
The quality of the body of evidence was assessed according to the GRADE Working Group criteria for diagnostic tests. For perfusion analysis, the overall quality was determined to be low and for wall motion analysis the overall quality was very low.
PMCID: PMC3377522  PMID: 23074389
25.  Open reduction and locking plate fixation of displaced proximal humerus fractures 
Indian Journal of Orthopaedics  2013;47(2):156-160.
Background:
Treatment of proximal humerus fractures is controversial and various operative modalities have been tried in the literature. The aim of the present study was to evaluate functional outcome and complication rate after open reduction and internal fixation of displaced proximal humerus fractures by proximal humerus locking plate.
Materials and Methods:
52 patients with displaced proximal humerus fractures treated with proximal humerus locking plate between May 2008 and October 2010 were included in the study. Fractures were classified according to Neer's classification into displaced 2-part, 3-part, and 4-part fractures. Patients were followed for a minimum period of 1 year. 11 patients had less than 1 year of followup and were not considered in the evaluation of final results. Forty one patients were considered for final evaluation. Functional evaluation was done according to the Constant-Murley scoring system. Constant score was compared between 2-part, 3-part, and 4-part fractures at final up and also between young (≤60 yrs) and old (>60 yrs).
Results:
11 patients had 2-part fractures, 22 patients had 3-part fractures, and 19 patients had 4-part fractures. The mean followup period was 15.21 ± 2.59 months. 65.8% (n = 27) patients had good to excellent result, 19.5% (n = 8) had fair, and 14.7% (n = 6) had poor result. Constant scores for 2-part (79.83 ± 6.95) and 3-part fractures (74.22 ± 12.53) were significantly superior to those of 4-part fractures (61.09 ± 14.29) (P value = 0.002 and 0.018, respectively). Difference between 2-part and 3-part fractures was not significant (P value = 0.623). There was no significant difference between younger (≤60) and older patients (>60). Complications encountered in this series were varus malreduction in 17% (n = 7), screw perforation in 10% (n = 4), plate impingement in 12% (n = 5), infection in 2% (n = 1), and nonunion in 2% (n = 1) of cases.
Conclusion:
Proximal humerus locking plate gives reliable fixation for 2-part and 3-part fractures. Its use in more complicated fracture patterns of 4-part fractures is associated with poor clinical outcome.
doi:10.4103/0019-5413.108903
PMCID: PMC3654465  PMID: 23682177
Proximal humerus locking plate; proximal humerus fracture; unstable fracture

Results 1-25 (619983)