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1.  Assessment of whole body MRI and sestamibi technetium-99m bone marrow scan in prediction of multiple myeloma disease progression and outcome: a prospective comparative study 
BMJ Open  2013;3(1):e002025.
Objectives
This study aims primarily to determine whether whole body MRI (WB-MRI) and Sestamibi Technetium-99m-bone marrow (MIBI) scans in the same patients produce the same estimate of disease load and location, and secondly, to study possible association between the bone disease detected by these scans and the effect on disease outcome and survival. Bone disease occurs in about 90% of multiple myeloma (MM) patients. There are no data comparing the new diagnostic modalities with WB-MRI and MIBI in MM.
Design
A prospective comparative study between WB-MRI and MIBI scans in assessing bone disease and outcome of MM.
Participants and methods
Sixty-two consecutive patients with confirmed MM underwent simultaneous WB-MRI (both axial T1 and turbo spin echo short tau inversion recovery (STIR)) and MIBI scans at a single institution from January 2010 to January 2011, and their survival status was determined in January 2012. The median age was 62 years (range 37–88) with a male-to-female ratio of 33 : 29.
Results
In vertebrae and long bones, MRI scan detected more disease compared with MIBI scan (p<0.001) but there was less difference in the skull (p=0.09). In the ribcage, the MIBI scan detected more lytic lesions of the ribs compared with MRI scan (p<0.001). Thirteen of the 62 patients died during the 24-month follow-up. Increased disease detected in all bones by both scans was associated with increased mortality risk (MIBI p=0.001; MRI-STIR p=0.044; but not MRI-T1 p=0.44). In all combined bone groups, the mean MIBI scan results provided a better prediction of mortality than MRI scan over the follow-up period (MRI-T1 vs MIBI p=0.019; MRI-STIR vs MIBI p=0.047).
Conclusions
Although WB-MRI detected more MM bone disease, MIBI scan predicted overall disease outcome and mortality better than MRI scan. Further studies to define optimum use of these imaging techniques are warranted.
Trial registration number
The study was registered prospectively in the Australian and New Zealand Clinical Trials Registry at http://www.ANZCTR.org.au under No: ACTRN12609000761268.
doi:10.1136/bmjopen-2012-002025
PMCID: PMC3549203  PMID: 23315438
Nuclear Medicine; Radiology & Imaging; Qualitative Research
2.  99mTc-MIBI Whole Body Scan: A Potentially Useful Technique for Evaluating Metabolic Bone Disease 
Metabolic bone disease due to hyperparathyroidism is characterized by increased bone resorption and new bone formation. 99mTc- hexakis-2-methoxyisobutylisonitrile (99mTc MIBI) accumulation is controlled by metabolic function and cell viability. To investigate, for the first time, the potential of whole body 99mTc MIBI scan for detecting, visually and with the aid of quantitative analysis, bony changes associated with hyperparathyroidism. Eighty-six patients with hyperparathyroidism, referred routinely for parathyroid localization, were included in this case-control prospective study. Each patient was injected with 20-25 mCi of 99mTc MIBI. Routine anterior cervico-thoracic images were obtained for parathyroid localization. Two extra whole body images were acquired and assessed visually and by drawing regions of interest over the mandible, sternum, femur, humeri, spine, and the soft tissue adjacent to the bone. The ratios of bone to soft tissue were calculated and compared to ratios drawn in a control group routinely referred for cardiac imaging and injected with 99mTc MIBI, after confirming the absence of any bone disease. The visual interpretation of the scans showed 48 patients to have increased bone uptake. Quantitative assessment showed significant difference between the mean ratios of the case and control groups. The Kruskal-Wallis test showed significant agreement between visual and quantitative ratios drawn from delayed right and left femora and left humerus images (P < 0.05). 99mTc MIBI whole body imaging is a potentially useful technique for assessing metabolic bone disease associated with hyperparathyroidism. Quantitative analysis helped in confirming the visual findings.
doi:10.4103/1450-1147.113934
PMCID: PMC3745637  PMID: 23961249
Hyperparathyroidism; metabolic bone disease; 99mTc- hexakis-2-methoxyisobutylisonitrile
3.  Dobutamine stress echocardiography versus quantitative technetium-99m sestamibi SPECT for detecting residual stenosis and multivessel disease after myocardial infarction 
Heart  2001;86(5):510-515.
OBJECTIVE—To compare the relative accuracy of dobutamine stress echocardiography (DSE) and quantitative technetium-99m sestamibi single photon emission computed tomography (mibi SPECT) for detecting infarct related artery stenosis and multivessel disease early after acute myocardial infarction.
DESIGN—Prospective study.
SETTING—University hospital.
METHODS—75 patients underwent simultaneous DSE and mibi SPECT at (mean (SD)) 5 (2) days after a first acute myocardial infarct. Quantitative coronary angiography was performed in all patients after imaging studies.
RESULTS—Significant stenosis (> 50%) of the infarct related artery was detected in 69 patients. Residual ischaemia was identified by DSE in 55 patients and by quantitative mibi SPECT in 49. The sensitivity of DSE and mibi SPECT for detecting significant infarct related artery stenosis was 78% and 70%, respectively, with a specificity of 83% for both tests. The combination of DSE and mibi SPECT did not change the specificity (83%) but increased the sensitivity to 94%. Mibi SPECT was more sensitive than DSE for detecting mild stenosis (73% v 9%; p = 0.008). The sensitivity of DSE for detecting moderate or severe stenosis was greater than mibi SPECT (97% v 74%; p = 0.007). Wall motion abnormalities with DSE and transient perfusion defects with mibi SPECT outside the infarction zone were sensitive (80% v 67%; NS) and highly specific (95% v 93%; NS) for multivessel disease.
CONCLUSIONS—DSE and mibi SPECT have equivalent accuracy for detecting residual infarct related artery stenosis of ⩾ 50% and multivessel disease early after acute myocardial infarction. DSE is more predictive of moderate or severe infarct related artery stenosis. Combined imaging only improves the detection of mild stenosis.


Keywords: myocardial infarction; dobutamine echocardiography; single photon emission computed tomography; SPECT; myocardial ischaemia
doi:10.1136/heart.86.5.510
PMCID: PMC1729965  PMID: 11602542
4.  A novel clinical indicator using cardiac technetium-99m sestamibi kinetics for evaluating cardiotoxicity in cancer patients treated with multiagent chemotherapy 
Background: Multiagent chemotherapy (MCT) has mitochondrial targets. Since technetium-99m-sestamibi (MIBI) is a marker of mitochondrial metabolism, cardiac MIBI uptake and MIBI washout rate (%WR) may detect MCT-induced cardiotoxicity. Methods: In 16 cancer patients on MCT for 10 months and in 14 non-cancer controls, cardiac MIBI uptake between early (30 min) and delayed (3 hours) post-injection planar images was measured as counts per pixel (cpp). The MIBI cardiac %WR was also measured. Results: When MCT patients and controls were compared, early and cardiac delayed MIBI uptake were greater in MCT patients (45 ± 12 cpp vs. 30 ± 4 cpp; p <0.04) and (30 ± 8 cpp vs. 25 ± 2 cpp; p < 0.02), but % WR did not change (12 ± 4% vs. 13 ± 3%; p = ns). However, in the MCT patients, the MIBI cardiac %WR was more rapid because it was obtained at the same time as in the control patients but from a greater amount of MIBI cardiac uptake. On 36-months follow-up, only MCT patients died of cardiac death. Overall survival risk parameters, only delayed cardiac MIBI uptake (Odds ratio = 1.7, p<0.001) and early cardiac MIBI uptake (Odds ratio = 1.2, p<0.02) were found to be significantly associated with cardiac mortality. Conclusions: In experimental studies, anticancer drugs elicit mitochondrial membrane hyperpolarization with passive cardiac MIBI uptake. In MCT patients, the increased cardiac MIBI uptake and rapid %WR compared with controls may reflect mitochondrial membrane dysfunction, pre-clinical cardiotoxicity and thus poor prognosis.
PMCID: PMC3499935  PMID: 23173103
Multiagent chemotherapy (MCT); technetium-99m-sestamibi (MIBI); mitochondrial metabolism; cardiotoxicity; cancer; multiagent chemotherapy
5.  Role of radiography, MRI and FDG-PET/CT in diagnosing, staging and therapeutical evaluation of patients with multiple myeloma 
Annals of Hematology  2009;88(12):1161-1168.
Multiple myeloma is a malignant B-cell neoplasm that involves the skeleton in approximately 80% of the patients. With an average age of 60 years and a 5-years survival of nearly 45% Brenner et al. (Blood 111:2516–2520, 35) the onset is to be classified as occurring still early in life while the disease can be very aggressive and debilitating. In the last decades, several new imaging techniques were introduced. The aim of this review is to compare the different techniques such as radiographic survey, multidetector computed tomography (MDCT), whole-body magnetic resonance imaging (WB-MRI), fluorodeoxyglucose positron emission tomography- (FDG-PET) with or without computed tomography (CT), and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy. We conclude that both FDG-PET in combination with low-dose CT and whole-body MRI are more sensitive than skeleton X-ray in screening and diagnosing multiple myeloma. WB-MRI allows assessment of bone marrow involvement but cannot detect bone destruction, which might result in overstaging. Moreover, WB-MRI is less suitable in assessing response to therapy than FDG-PET. The combination of PET with low-dose CT can replace the golden standard, conventional skeletal survey. In the clinical practise, this will result in upstaging, due to the higher sensitivity.
doi:10.1007/s00277-009-0829-0
PMCID: PMC2763177  PMID: 19763570
Multiple myeloma; Radiography; MDCT; WB-MRI; FDG-PET/CT; 99mTc-MIBI
6.  99mTc-MIBI scan in mammary Pagets disease: a case report. 
Journal of Korean Medical Science  1999;14(6):675-678.
Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) uptake is known to be increased in breast cancer because of increased blood flow from angiogenesis and heightened metabolism. We performed a 99mTc-MIBI scan in a patient with mammary Paget's disease. The patient had underlying invasive cancer in the same side of the breast. 99mTc-MIBI scan exhibited a scintigraphic image of the uptake from the invasive cancer lesion located deeply in the breast toward the epidermis. 99mTc-MIBI showed an uptake in the deeply located invasive cancer lesion as well as nipple lesion. Especially, the delayed phase of Tc-MIBI scan demonstrated the tumor site more accurately. In conclusion, 99mTc-MIBI scan could be a useful adjunct to clinical decision making in the management of Paget's disease of the breast.
PMCID: PMC3054442  PMID: 10642948
7.  The use of 99mTc-MIBI scanning in multiple myeloma. 
British Journal of Cancer  1996;74(11):1815-1820.
Tc-99m 2 methoxy-isobutyl-isonitrile (99mTc-MIBI), also called Sestamibi, is a safe and effective scanning agent in solid tumours. Its use in imaging lesions in multiple myeloma has been studied in 21 patients with either multiple myeloma (19/21) or monoclonal gammopathy of undetermined significance (MGUS) (2/ 21). 99mTc-MIBI scanning was positive in 14 patients, 13 with active myeloma and one patient with MGUS showing possible transformation to a more accelerated phase. In seven patients 99mTc-MIBI scanning was negative. In four of them, the result was unexpected, as they had the features of active myeloma. All four were either primarily or secondarily resistant to chemotherapy, with high total cumulative doses of doxorubicin. Overexpression of P-glycoprotein associated with multidrug resistance could be a factor, as it has been shown that 99mTc-MIBI is actively eliminated from the cell by P-glycoprotein. With this assumption, sensitivity of the scanning technique in this series is 100%, and the specificity 88%. No toxicity was experienced by any patient. 99mTc-MIBI scanning is a useful adjunct to the investigation of multiple myeloma, and may have potential as an in vivo test for multidrug resistance.
Images
PMCID: PMC2077234  PMID: 8956799
8.  Transient Ischemic Dilation for Coronary Artery Disease in Quantitative analysis of Same-day Sestamibi Myocardial Perfusion SPECT 
Journal of Nuclear Cardiology  2012;19(3):465-473.
Background
Transient ischemic dilation (TID) of the left ventricle in Myocardial Perfusion SPECT (MPS) has been shown to be a clinically useful marker of severe coronary artery disease (CAD). However, TID has not been evaluated for 99mTc-sestamibi rest/stress protocols (Mibi-Mibi). We aimed to develop normal limits and evaluate diagnostic power of TID ratio for Mibi-Mibi scans.
Methods
TID ratios were automatically derived from static stress/rest MPS (TID) and gated stress/rest MPS from the end-diastolic phase (TIDed) in 547 patients who underwent Mibi-Mibi scans (215 patients with correlating coronary angiography and 332 patients with low likelihood (LLk) of CAD). Scans were classified as severe (≥70% stenosis in proximal left anterior descending artery (pLAD) or left main (LM), or ≥90% in ≥2 vessels), mild to moderate (≥90% stenosis in 1 vessel or ≥70%-90% in ≥1 vessel except pLAD or LM), and normal (<70% stenosis or LLk group). Another classification based on the angiographic Duke prognostic CAD index (DI) was also applied: DI < 30 or LLk group, 30 ≤ DI < 50 and DI ≥ 50.
Results
The upper normal limits were 1.19 for TID and 1.23 for TIDed as established in 259 LLk patients. Both ratios increased with disease severity (P<.0001). Incidence of abnormal TID increased from 2% in normal patients to > 36% in patients with severe CAD. Similarly, when DI was used to classify disease severity, the average ratios showed significant increasing trend with DI increase [P < 0.003]; incidence of abnormal TID also increased with increasing DI. The incidence of abnormal TID in the group with high perfusion scores significantly increased compared to the group with low perfusion scores (stress total perfusion deficit – TPD <3%) (P <.0001). The sensitivity for detecting severe CAD improved for TID when added to mild to moderate perfusion abnormality (3% ≤ TPD < 10%): 71% vs. 64%: P<0.05; and trended to improve for TIDed/ TIDes: 69% vs. 64%: P=0.08, while the accuracy remained consistent if abnormal TID was considered as a marker in addition to stress TPD. Similar results were obtained when DI was used for the definition of severe CAD (sensitivity: 76% vs. 66% [P < 0.05] when TID was combined with stress TPD.
Conclusion
TID ratios obtained from gated or ungated Mibi-Mibi MPS and are useful markers of severe CAD.
doi:10.1007/s12350-012-9527-8
PMCID: PMC3377488  PMID: 22399366
Single photon emission computed tomography; myocardial perfusion imaging; sestamibi; transient ischemic dilation
9.  Assessment of myocardial perfusion and contractile function by inotropic stress Tc-99m sestamibi SPECT imaging and echocardiography for optimal detection of multivessel coronary artery disease 
Heart  1998;79(3):274-280.
Objective—To assess whether inotropic stress myocardial perfusion imaging, echocardiography, or a combination of the two could enhance the detection of multivessel disease, over and above clinical and exercise electrocardiographic data.
Design—100 consecutive patients investigated by exercise electrocardiography and diagnostic coronary arteriography underwent simultaneous inotropic stress Tc-99m sestamibi SPECT (MIBI) imaging and echocardiography. MIBI imaging and echocardiographic data were analysed using a 12 segment left ventricular model, and each segment was ascribed to a particular coronary artery territory. The presence of perfusion defects with MIBI imaging or of wall thickening abnormality with echocardiography in at least two coronary artery territories at peak stress was taken as diagnostic of multivessel disease. Arteriographic evidence of ⩾ 50% stenosis was considered significant.
Results—56 patients had multivessel disease. The sensitivity of the combination of MIBI imaging and echocardiography for detecting this was greater than either MIBI imaging or echocardiography alone (82%, 68%, and 68%, respectively; p = 0.005). Clinical and exercise electrocardiographic variables gave an R2 value of 18.2% for predicting multivessel disease. The addition of either MIBI imaging (R2 = 29.2%; p = 0.002) or echocardiography (R2 = 28.8%; p < 0.001) enhanced the detection of multivessel disease, and the inclusion of both had further incremental value (R2 = 34.8%; p = 0.003). Age (p = 0.03), MIBI imaging (p = 0.007), and echocardiography (p = 0.001) were independent predictors of multivessel disease.
Conclusions—The assessment of both myocardial perfusion and contractile function by simultaneous inotropic stress MIBI imaging and echocardiography optimises the non-invasive detection of multivessel disease.

 Keywords: multivessel disease;  inotropic stress;  SPECT imaging;  echocardiography
PMCID: PMC1728627  PMID: 9602662
10.  Primary Hyperparathyroidism Patients with Positive Preoperative Sestamibi Scan and Negative Ultrasound Are More Likely to Have Posteriorly Located Upper Gland Adenomas (PLUGs) 
Annals of Surgical Oncology  2011;18(6):1717-1722.
Background
Standard preoperative imaging for primary hyperparathyroidism usually includes sestamibi scanning (MIBI) and ultrasound (US). In a subset of patients with a positive MIBI and a negative US, we hypothesize that the parathyroid adenomas are more likely to be located posteriorly in the neck, where anatomically they are more difficult to detect by US.
Methods
We retrospectively reviewed the records of 661 patients treated for primary hyperparathyroidism between 2004 and 2009 at a tertiary referral center. We included patients who for their first operation had a MIBI that localized a single lesion in the neck and an US that found no parathyroid adenoma. We excluded patients with persistent or recurrent hyperparathyroidism, and patients with MIBIs that were negative, that had more than one positive focus, or that had foci outside of the neck. Sixty-six cases were included in the final analysis.
Results
A total of 54 patients (83%) had a single adenoma, 4 (6%) had double adenomas, and 7 (11%) had hyperplasia. Thirty-three patients (51%) had a single upper gland adenoma; 19 of these (58%) were posteriorly located upper gland adenomas (PLUGs). PLUGs occurred more often on the right side than on the left (P = 0.048, Fisher’s test). PLUGs were also larger than other single adenomas (mean 1.85 vs. 1.48 cm, P = 0.021, t-test). Seventy-six percent of patients successfully underwent a unilateral or focused exploration. Six patients (9%) had persistent disease, which is double our group’s overall average (4–5%).
Conclusions
Primary hyperparathyroid patients with preoperative positive MIBI and negative US are more likely to have PLUGs.
doi:10.1245/s10434-010-1493-2
PMCID: PMC3087871  PMID: 21207169
11.  Role of Tc-99m MIBI in the evaluation of single pulmonary nodules: a preliminary report 
Thorax  2000;55(1):60-62.
BACKGROUND—Survival in bronchial carcinoma is closely related to the stage of the disease at the time of diagnosis and a single pulmonary nodule represents a potentially curable stage. This study was conducted to assess the feasibility of using Tc-99m labelled 2-methoxy isobutyl isonitrile (MIBI) to differentiate benign from malignant single pulmonary nodules.
METHODS—A prospective study was conducted in the outpatient pulmonary clinic at the Cleveland Clinic Foundation. Twenty five patients with single pulmonary nodules considered indeterminate by their physicians and undergoing a procedure for tissue diagnosis were evaluated by Tc-99m MIBI SPECT scanning prior to definitive testing. Assessment of MIBI uptake was done qualitatively (subjectively) and quantitatively and correlated with the histopathology and nodule size.
RESULTS—Of the 21 patients with malignant lesions, 18 had increased uptake of MIBI corresponding to the location of the nodule and were considered positive. The predominant tumour types were large cell (n = 5) and adenocarcinoma (n = 10). All four patients with benign lesions had negative MIBI scans. For malignancy the overall specificity was 100%, sensitivity was 85.7%, positive predictive value was 100%, and negative predictive value was 57%. Quantitative uptake of MIBI correlated with the diameter of the nodule with a correlation coefficient of 0.61 by Spearman's rank sum test. This relationship was statistically significant (p = 0.02).
CONCLUSION—This preliminary study suggests that Tc-99m MIBI has a very high specificity and positive predictive value for malignant single pulmonary nodules and might be a useful non-invasive diagnostic modality in their management.


doi:10.1136/thorax.55.1.60
PMCID: PMC1745583  PMID: 10607803
12.  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
13.  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
14.  99mTc-3P4-RGD2 Scintimammography in the Assessment of Breast Lesions: Comparative Study with 99mTc-MIBI 
PLoS ONE  2014;9(9):e108349.
Purpose
To compare the potential application of 99mTc-3P-Arg-Gly-Asp (99mTc-3P4-RGD2) scintimammography (SMM) and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) SMM for the differentiation of malignant from benign breast lesions.
Method
Thirty-six patients with breast masses on physical examination and/or suspicious mammography results that required fine needle aspiration cytology biopsy (FNAB) were included in the study. 99mTc-3P4-RGD2 and 99mTc-MIBI SMM were performed with single photon emission computed tomography (SPECT) at 60 min and 20 min respectively after intravenous injection of 738±86 MBq radiotracers on a separate day. Images were evaluated by the tumor to non-tumor localization ratios (T/NT). Receiver operating characteristic (ROC) curve analysis was performed on each radiotracer to calculate the cut-off values of quantitative indices and to compare the diagnostic performance for the ability to differentiate malignant from benign diseases.
Results
The mean T/NT ratio of 99mTc-3P4-RGD2 in malignant lesions was significantly higher than that in benign lesions (3.54±1.51 vs. 1.83±0.98, p<0.001). The sensitivity, specificity, and accuracy of 99mTc-3P4-RGD2 SMM were 89.3%, 90.9% and 89.7%, respectively, with a T/NT cut-off value of 2.40. The mean T/NT ratio of 99mTc-MIBI in malignant lesions was also significantly higher than that in benign lesions (2.86±0.99 vs. 1.51±0.61, p<0.001). The sensitivity, specificity and accuracy of 99mTc-MIBI SMM were 87.5%, 72.7% and 82.1%, respectively, with a T/NT cut-off value of 1.45. According to the ROC analysis, the area under the curve for 99mTc-3P4-RGD2 SMM (area = 0.851) was higher than that for 99mTc-MIBI SMM (area = 0.781), but the statistical difference was not significant.
Conclusion
99mTc-3P4-RGD2 SMM does not provide any significant advantage over the established 99mTc-MIBI SMM for the detection of primary breast cancer. The T/NT ratio of 99mTc-3P4-RGD2 SMM was significantly higher than that of 99mTc-MIBI SMM. Both tracers could offer an alternative method for elucidating non-diagnostic mammograms.
doi:10.1371/journal.pone.0108349
PMCID: PMC4176966  PMID: 25250628
15.  Clinical value of technetium-99m-labeled octreotide scintigraphy in local recurrent or metastatic medullary thyroid cancers: a comparison of lesions with 18F-FDG-PET and MIBI images 
Nuclear Medicine Communications  2013;34(12):1190-1195.
Aim
Various studies have been conducted for determining the most optimal method for the early diagnosis of local recurrent or distant metastatic thyroid cancers. The aim of this study was to evaluate the clinical utility of technetium-99m (Tc-99m)-labeled octreotide derivatives in the detection of recurrence or distant metastases in medullary thyroid cancer patients and to compare the lesions with those detected using 18F-fluorodeoxyglucose (18F-FDG)-PET and Tc-99m MIBI studies in the same patient group.
Patients and methods
Sixteen medullary thyroid cancer patients [two male and 14 female; mean age 52.0±14.1 years (range 13–72 years)] were included in this study. All patients underwent a whole-body scan 1 and 4 h after injection with octreotide derivatives and single photon emission computed tomography images were taken of the sites suspicious for metastasis. The lesions seen in Tc-99m HYNIC octreotide studies were compared with those seen in 18F-FDG-PET and Tc-99m MIBI studies.
Results
Among the Tc-99m-labeled octreotide scintigraphy studies, nine were evaluated as true positive (56.2%) and one was evaluated as false positive (6.2%); six were false negative (37.5%). In 16 patients, the total number of lesions seen on octreotide scintigraphy was 21. Thirteen of the 16 patients underwent 18F-FDG-PET imaging. Of the 13 patients studied, 10 showed true-positive (76.9%) and three showed false-negative (23.1%) results. The total number of lesions seen on 18F-FDG-PET was 23. The Tc-99m MIBI study yielded positive results in seven of 16 patients (43.7%) and negative results in nine patients (56.3%). The total number of lesions on Tc-99m MIBI was 12.
Conclusion
The Tc-99m-labeled somatostatin receptor scintigraphy analogs HYNIC-tyrosine octreotide and HYNIC-TATE are useful imaging alternatives in somatostatin receptor-expressing thyroid cancers. Radiolabeling using these analogs is easy and they are readily available for routine use.
doi:10.1097/MNM.0000000000000006
PMCID: PMC3815136  PMID: 24121313
18F-fluorodeoxyglucose-PET; HYNIC-TATE; HYNIC-tyrosine octreotide; octreotide scintigraphy; Tc-99m MIBI
16.  Pituitary Incidentalomas Detected with Technetium-99m MIBI in Patients with Suspected Parathyroid Adenoma: Preliminary Results 
Tc-99m MIBI (MIBI) is a cationic lipophilic agent, which has traditionally been used for myocardial perfusion scintigraphy, detection and monitoring of different benign and malignant tumors. The objective of this study was to evaluate the frequency of pituitary incidentalomas detected on MIBI scans performed on patients with suspected parathyroid adenomas and to provide semiquantitative analysis of tracer uptake in the pituitary region. Tomographic images of MIBI scans on 56 patients with suspected parathyroid adenomas (2006–2007) were analyzed retrospectively. Semiquantitative analysis of abnormal uptake was performed by drawing identical regions of interest (ROI) over the pituitary area and the normal brain on one transverse section that demonstrates the lesion most clearly. Pituitary uptake to normal brain uptake ratio was calculated in all cases. We found statistically significant differences of MIBI uptake in patients with pituitary adenomas, mean ratio: 29.78±12.17 (median 29.77, and range 19-41), compared with patients with no pathologic changes in this region, mean ratio was 5.88±1.82 (median was 5.95 and range 2.0- 9.2). As the groups are too small for statistical analysis, these results need to be confirmed in a larger cohort and should include more detailed biochemical correlation. MIBI parathyroid scintigraphy should be taken into account as a potential source of identifying pituitary incidentalomas. Clinical significance of these findings needs further evaluation.
doi:10.4103/1450-1147.98721
PMCID: PMC3425228  PMID: 22942774
Parathyroid adenoma; pituitary adenoma; pituitary incidentaloma; Tc-99m MIBI scintigraphy
17.  The Diagnostic Value of Tc-99m MIBI Gated Myocardial Perfusion SPECT in Detection of Silent Myocardial Ischemia in Asymptomatic Patients with Type 2 Diabetes Mellitus 
Objective:
In this study, we aimed to evaluate the diagnostic value of Technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) gated myocardial perfusion SPECT (MPS) in the detection of coronary artery disease (CAD) and silent myocardial ischemia (SMI) in patients with asymptomatic type 2 diabetes mellitus (DM).
Materials and Methods:
For this purpose, 35 patients with type 2 DM and 15 volunteers with no cardiac symptoms (control group) were included in this study. Exercise tolerance tests (ETT), echocardiography and Tc-99m MIBI gated MPS were performed in patients and volunteers. Computed tomography coronary angiography (CTCA) was performed in patients with coronary ischemia or infarct detected by Tc-99m MIBI gated MPS. The results were analyzed and compared visually and statistically.
Results:
The present study revealed a high rate of silent myocardial ischemia (25.71%, N=9) in 35 patients with type 2 DM. Severe CAD in CTCA was detected in four of nine patients with ischemia or infarct by Tc-99m MIBI gated MPS (44.4%). Left ventricular diastolic dysfunction, ischemic pattern and high risk of CAD were detected in the same four patients by echocardiography, ETT and biochemical analysis, respectively. At the end of the statistical evaluation, we found that Tc-99m MIBI gated MPS showed significant correlations with CTCA, echocardiography, ETT, Hba1c level, risk of CAD and diabetic age in diabetic patients with CAD.
Conclusion:
We propose that Tc-99m MIBI gated MPS is a reliable and non-invasive method that can be used to detect silent myocardial ischemia and CAD in patients with type 2 DM.
PMCID: PMC4261682  PMID: 25610029
Diabetes Mellitus; Gated SPECT; Myocardial Ischemia; Tc-99m MIBI; Gated SPECT; Type 2
18.  The Relationship Between Technetium-99m-Methoxyisobutyl Isonitrile Parathyroid Scintigraphy and Hormonal and Biochemical Markers in Suspicion of Primary Hyperparathyroidism 
Objective: Technetium-99m-methoxyisobutyl isonitrile (Tc-99m MIBI) has been widely used to evaluate hyperfunctioning autonomous parathyroid glands in patients with elevated intact parathyroid hormone (iPTH) and/or calcium (Ca) level. The aim of this study was to evaluate the relationship between Tc-99m MIBI parathyroid scintigraphy and hormonal and biochemical markers in suspicion of primary hyperparathyroidism (PHPT).
Material and Methods: Dual-phase Tc-99m MIBI parathyroid scintigraphy and total serum iPTH, Ca, phosphorus (P) and albumin measurements were performed in 60 patients (52 females, 8 males; mean age, 59.38±12.51 years; range, 34 to 86 years) with suspicion of PHPT.
Results: The iPTH median level was 160.3 pg/mL (47.8 to 782.6). Thirty-five of the patients had surgical resection of hyperfunctioning parathyroid glands. Of the 35 patients, parathyroid gland pathology was detected in 30 patients using scintigraphic examination. Tc-99m MIBI parathyroid scintigraphy was negative in 30 patients. The iPTH, Ca and P levels were significantly different between in the Tc-99m MIBI positive group and the negative group, respectively: For iPTH, 202.1 (47.8-782.6) pg/mL versus 111.6 (80.1-373) pg/mL; p<0.001. For Ca, 11.7±1.15 mg/dL versus 10.3±1.05 mg/dL; p<0.001 and for P levels, 2.46±0.62 mg/dL versus 3.40±0.70 mg/dL; p<0.001). There was no significant difference in serum albumin levels between the MIBI positive and MIBI negative groups (4.25±0.27 g/dL versus 4.25±0.41 g/dL; p>0.05). Tc-99m MIBI parathyroid scintigraphy showed good correlation with iPTH level and histopathological diagnosis. Sensitivity and specificity was found 83.3% and 76.7%, respectively at the level of iPTH>147.7pg/mL.
Conclusion: Tc-99m MIBI parathyroid scintigraphy is most likely to produce identification and localization of a parathyroid adenoma when both iPTH and Ca are elevated as well as decreased P levels.
Conflict of interest:None declared.
doi:10.4274/Mirt.21931
PMCID: PMC3629790  PMID: 23610725
Technetium-99m sestamibi; primary hyperparathyroidism; parathyroid hormone; calcium; phosphorus
19.  Preoperative localization of parathyroid lesion: diagnostic usefulness of color doppler ultrasonography 
Introduction
Recently, minimally invasive parathyroidectomy (MIP) has been developed and is gaining popularity among surgeons. For this reason, preoperative localization is playing an important role to detect the precise location of the affected gland and to increase the success rate.
Material and methods
From June 2007 to June 2011, 56 consecutive patients (11 men and 45 women) with primary or secondary hyperparathyroidism in our center underwent Gray scale, color Doppler and 99m-Tc MIBI scan prior to operative management of parathyroid lesions.
Results
The sensitivity, specificity and accuracy of US and MIBI scan for pHPT was 88%, 94%, 91% and 70%, 100% and 85% respectively. In patients with sHPT, the sensitivity, specificity and accuracy of US and MIBI scan was 54%, 93%, 76% and 25%, 100% and 72.9% respectively. The overall sensitivity of combined US and MIBI scan in pHPT and sHPT was 97% and 45% respectively. The overall sensitivity, specificity and accuracy of CDUS in diagnosis of parathyroid lesions in pHPT and sHPT is 97%, 100%, 98.6% and 62%, 100% and 83% respectively.
Conclusion
The overall sensitivity and specificity of US and MIBI in preoperative localization of parathyroid adenoma in sHPT is lower than pHPT and performing CDUS can increases the overall sensitivity and specificity of imaging methods in accurate localization of parathyroid lesion.
PMCID: PMC3272690  PMID: 22328952
Preoperative localization; parathyroid lesion; diagnosis; color doppler; ultrasonography
20.  Selection of the optimal stress test for the diagnosis of coronary artery disease 
Heart  1998;80(4):370-376.
Objective—To compare the value and limitations of exercise testing, dipyridamole echocardiography, dobutamine-atropine echocardiography, and MIBI-SPECT (technetium-99m methoxyisobutyl nitrile single photon emission computed tomography) during dobutamine infusion in the diagnosis of coronary artery disease.
Design—The performance of these four tests was assessed in random order on a consecutive cohort of patients. The presence or absence of coronary artery disease was confirmed by coronary angiography.
Setting—Two tertiary care and university centres.
Patients—102 consecutive patients with chest pain and no previous history of coronary artery disease. Ten patients with left bundle branch block were excluded for further analysis of exercise testing and scintigraphy results.
Results—MIBI-SPECT was the most sensitive (87%) but the least specific test (70%). Exercise stress testing had a sensitivity of 66%, which increased to 80% when patients with inconclusive results were excluded. Dipyridamole and dobutamine echocardiography had similar sensitivity (81%, 78%) and specificity (94%, 88%). All four tests had similar accuracy and positive and negative predictive values. Agreement between the echocardiographic techniques was excellent (detection of coronary artery disease 87%, κ = 0.72; regional analysis 93%, κ = 0.72; diagnosis of the "culprit" vessel 95%, κ = 0.92), and it was good between echocardiographic techniques and MIBI-SPECT (diagnosis of the culprit vessel 90%, κ = 0.84 with dobutamine and 92%, κ = 0.85 with dipyridamole).
Conclusions—Exercise stress testing has a sensitivity comparable to other tests in patients capable of exercising and with no basal electrical abnormalities. The greatest sensitivity is offered by MIBI-SPECT and the greatest specificity is obtained with stress echocardiography. Redundant information is obtained with dipyridamole echocardiography, dobutamine echocardiography, and MIBI-SPECT.

 Keywords: coronary artery disease;  dipyridamole;  dobutamine;  scintigraphy
PMCID: PMC1728805  PMID: 9875115
21.  Bromocriptine enhances the uptake of 99mTc-MIBI in patients with hepatocellular carcinoma 
Journal of Biomedical Research  2012;26(3):165-169.
99mTc-methoxyisobutyl isonitrile (MIBI) is a suitable transport substrate for the multidrug resistance gene product P-glycoprotein (P-gp) and widely used for tumor imaging. Bromocriptine has been shown to inhibit the ATPase activity and the function of P-gp. We hypothesized that bromocriptine could promote the accumulation of MIBI by inhibiting P-gp activities, a feature that can be taken advantage of for enhancing 99mTc-MIBI imaging. In the current study, we sought to investigate whether bromocriptine enhanced the uptake of 99mTc-MIBI in hepatocellular carcinoma patients. Sixty primary hepatocellular carcinoma patients received 99mTc-MIBI single photon emission computer tomgraphy (SPECT) prior to surgery. 99mTc-MIBI SPECT was performed 15 and 120 min after injection of 20 mCi 99mTc-MIBI, and early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of 99mTc-MIBI were obtained. In addition, a second 99mTc-MIBI SPECT was performed according to the same method 48 h after bromocriptine administration. We found that, prior to bromocriptine administration, significant MIBI uptake in tumor lesions was noted in only 10 (16.7%, 10/60) patients with hepatocellular carcinoma. No significant MIBI uptake was observed in the tumor lesions of the remaining 50 (83.3%, 50/60) hepatocellular carcinoma patients. Following bromocriptine administration, all the patients without apparent MIBI uptake demonstrated significant MIBI uptake on 99mTc-MIBI SPECT (P < 0.05). Our findings indicate that bromocriptine enhances the uptake of 99mTc-MIBI in patients with hepatocellular carcinoma.
doi:10.7555/JBR.26.20110075
PMCID: PMC3596066  PMID: 23554746
liver cancer; multidrug resistance; P-glycoprotein; 99mTc-MIBI; bromocriptine
22.  Assessment of Myocardial Scar; Comparison Between 18F-FDG PET, CMR and 99Tc-Sestamibi 
Objective:
Patients with heart failure and ischaemic heart disease may obtain benefit from revascularisation if viable dysfunctional myocardium is present. Such patients have an increased operative risk, so it is important to ensure that viability is correctly identified. In this study, we have compared the utility of 3 imaging modalities to detect myocardial scar.
Design:
Prospective, descriptive study.
Setting:
Tertiary cardiac centre.
Patients:
35 patients (29 male, average age 70 years) with coronary artery disease and symptoms of heart failure (>NYHA class II).
Intervention:
Assessment of myocardial scar by 99Tc-Sestamibi (MIBI), 18F-flurodeoxyglucose (FDG) and cardiac magnetic resonance (CMR).
Outcome Measure:
The presence or absence of scar using a 20-segment model.
Results:
More segments were identified as nonviable scar using MIBI than with FDG or CMR. FDG identified the least number of scar segments per patient (7.4 +/− 4.8 with MIBI vs. 4.9 +/− 4.2 with FDG vs. 5.8 +/− 5.0 with CMR, p = 0.0001 by ANOVA). The strongest agreement between modalities was in the anterior wall with the weakest agreement in the inferior wall. Overall, the agreement between modalities was moderate to good.
Conclusion:
There is considerable variation amongst these 3 techniques in identifying scarred myocardium in patients with coronary disease and heart failure. MIBI and CMR identify more scar than FDG. We recommend that MIBI is not used as the sole imaging modality in patients undergoing assessment of myocardial viability.
PMCID: PMC2872587  PMID: 20508767
heart failure; hibernation; PET; MIBI; CMR
23.  Incidental uptake of 18F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer 
Radiology and Oncology  2014;48(3):228-234.
Background
Positron emission tomography-computed tomography (PET/CT) with 18F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases.
Results
In 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histology in two cases, correlative imaging with MRI in four cases, 99mTc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumours consisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma.
Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis.
Conclusions
To the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroid glands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma after surgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. In these potential indications, comparative studies with reference PET tracers or with 99mTc-sestaMIBI in case of hyperparathyroidism could be undertaken.
doi:10.2478/raon-2013-0075
PMCID: PMC4110078  PMID: 25177236
FCH, PET/CT; incidentaloma; meningioma; pituitary adenoma; hyperparathyroidism; thyroid adenoma
24.  Positron emission tomography/computed tomography imaging of brown tumors mimicking multiple skeletal metastases in patient with primary hyperparathyroidism 
Brown tumors of bone are highly vascular, lytic bone lesions representing a reparative cellular process rather than a neoplastic process usually seen in patients with hyperparathyroidism. These tumors can behave aggressively and be destructive. We report a 49-year-old male patient who was admitted to our hospital with a long-term history of right shoulder and right hip pain. Multiple lytic and destructive bone lesions were found in X-ray graphy and CT images. These bone lesions mimicked multiple skeletal metastatic lesions and seemed to be those of the terminal stage of malignancy. PET scan was requested for the evaluation of FDG uptake of these lesions and to search the unknown primary tumor site. Positron emission tomography/computed tomography (PET/CT) images showed multiple hypermetabolic malignant or metastatic FDG avid bone lesions in skeletal system. However the biopsy results revealed no signs of malignancy and laboratory data showed elevated serum calcium, alkaline phosphatase, parathyroid hormone, low serum phosphate and parathyroid scintigraphy was performed. Adenoma in the left parathyroid gland was seen with Tc-99m MIBI parathyroid scintigraphy. Pathological results confirmed the diagnosis of parathyroid adenoma. Brown tumor is the potential cause of false-positive result in evaluation of a patient for unknown primary tumor or skeletal metastases with PET/CT imaging.
doi:10.4103/2230-8210.100682
PMCID: PMC3475922  PMID: 23087882
Brown tumor; hyperparathyroidism; flourodeoxyglocose; positron emission tomography/computed tomography
25.  Limitations of Tc99m-MIBI-SPECT Imaging Scans in Persistent Primary Hyperparathyroidism 
World Journal of Surgery  2010;35(1):128-139.
Background
In primary hyperparathyroidism (PHPT) the predictive value of technetium 99m sestamibi single emission computed tomography (Tc99m-MIBI-SPECT) for localizing pathological parathyroid glands before a first parathyroidectomy (PTx) is 83–100%. Data are scarce in patients undergoing reoperative parathyroidectomy for persistent hyperparathyroidism. The aim of the present study was to determine the value of Tc99m-MIBI-SPECT in localizing residual hyperactive parathyroid tissue in patients with persistent primary hyperparathyroidism (PHPT) after initial excision of one or more pathological glands.
Method
We retrospectively evaluated the localizing accuracy of Tc99m-MIBI-SPECT scans in 19 consecutive patients with persistent PHPT who had a scan before reoperative parathyroidectomy. We used as controls 23 patients with sporadic PHPT who had a scan before initial surgery.
Results
In patients with persistent PHPT, Tc99m-MIBI-SPECT accurately localized a pathological parathyroid gland in 33% of cases before reoperative parathyroidectomy, compared to 61% before first PTx for sporadic PHPT. The Tc99m-MIBI-SPECT scan accurately localized intra-thyroidal glands in 2 of 7 cases and a mediastinal gland in 1 of 3 cases either before initial or reoperative parathyroidectomy.
Conclusions
Our data suggest that the accuracy of Tc99m-MIBI-SPECT in localizing residual hyperactive glands is significantly lower before reoperative parathyroidectomy for persistent PHPT than before initial surgery for sporadic PHPT. These findings should be taken in consideration in the preoperative workup of patients with persistent primary hyperparathyroidism.
doi:10.1007/s00268-010-0818-4
PMCID: PMC3006642  PMID: 20957360

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