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1.  SAR and Temperature: Simulations and Comparison to Regulatory Limits for MRI 
To present and discuss numerical calculations of the specific absorption rate (SAR) and temperature in comparison to regulatory limits. While it is possible to monitor whole-body or whole-head average SAR and/or core body temperature during MRI in practice, this is not generally true for local SAR values or local temperatures throughout the body. While methods of calculation for SAR and temperature are constantly being refined, methods for interpreting results of these calculations in light of regulatory limits also warrant discussion.
Materials and Methods
Numerical calculations of SAR and temperature for the human head in a volume coil for MRI at several different frequencies are presented.
Just as the field pattern changes with the frequency, so do the temperature distribution and the ratio of maximum local SAR (in 1-g or 10-g regions) to whole-head average SAR. In all of the cases studied here this ratio is far greater than that in the regulatory limits, indicating that existing limits on local SAR will be exceeded before limits on whole-body or whole-head average SAR are reached.
Calculations indicate that both SAR and temperature distributions vary greatly with B1 field frequency, that temperature distributions do not always correlate well with SAR distributions, and that regulatory limits on local temperature may not be exceeded as readily as those on local SAR.
PMCID: PMC4040525  PMID: 17654736
MRI; SAR; temperature, safety; simulations
2.  Venous and Arterial Flow Quantification, are Equally Accurate and Precise with Parallel Imaging Compressed Sensing 4D Phase Contrast MRI 
To evaluate precision and accuracy of parallel-imaging compressed-sensing 4D phase contrast (PICS-4DPC) MRI venous flow quantification in children with patients referred for cardiac MRI at our children’s hospital.
Materials and Methods
With IRB approval and HIPAA compliance, 22 consecutive patients without shunts underwent 4DPC as part of clinical cardiac MRI examinations. Flow measurements were obtained in the superior and inferior vena cava, ascending and descending aorta and the pulmonary trunk. Conservation of flow to the upper, lower and whole body was used as an internal physiologic control. The arterial and venous flow rates at each location were compared with paired t-tests and F-tests to assess relative accuracy and precision.
Arterial and venous flow measurements were strongly correlated for the upper (ρ=0.89), lower (ρ=0.96) and whole body (ρ=0.97); net aortic and pulmonary trunk flow rates were also tightly correlated (ρ=0.97). There was no significant difference in the value or precision of arterial and venous flow measurements in upper, lower or whole body, though there was a trend toward improved precision with lower velocity-encoding settings.
With PICS-4DPC MRI, the accuracy and precision of venous flow quantification are comparable to that of arterial flow quantification at velocity-encodings appropriate for arterial vessels.
PMCID: PMC3582745  PMID: 23172846
Cardiovascular; 4D flow; flow quantification; compressed sensing; parallel imaging
3.  Combination of Multichannel Single-Voxel MRS Signals Using Generalized Least Squares 
To propose using the generalized least square (GLS) algorithm for combining multichannel single-voxel MRS signals.
Materials and Methods
Phantom and in vivo brain MRS experiments on a 7 T scanner equipped with a 32-channel receiver coil, as well as Monte Carlo simulations, were performed to compare the coefficient of variation (CV) of the GLS method with those of two recently reported spectral combination methods.
Compared to the two existing methods, the GLS method significantly reduced CV values for the simulation, phantom, and in vivo experiments.
The GLS method can lead to improved precision of peak quantification.
PMCID: PMC3582859  PMID: 23172656
MRS; multichannel coil; SNR; noise correlation; generalized least squares; GLS
4.  Regional Myocardial Blood Volume and Flow: First-Pass MR Imaging with Polylysine-Gd-DTPA 
The authors investigated the utility of an intravascular magnetic resonance (MR) contrast agent, poly-L-lysine-gadolinium diethylenetriaminepentaacetic acid (DTPA), for differentiating acutely ischemic from normally perfused myocardium with first-pass MR imaging. Hypoperfused regions, identified with microspheres, on the first-pass images displayed significantly decreased signal intensities compared with normally perfused myocardium (P < .0007). Estimates of regional myocardial blood content, obtained by measuring the ratio of areas under the signal intensity-versus-time curves in tissue regions and the left ventricular chamber, averaged 0.12 mL/g ± 0.04 (n = 35), compared with a value of 0.11 mL/g ± 0.05 measured with radiolabeled albumin in the same tissue regions. To obtain MR estimates of regional myocardial blood flow, in situ calibration curves were used to transform first-pass intensity-time curves into content-time curves for analysis with a multiple-pathway, axially distributed model. Flow estimates, obtained by automated parameter optimization, averaged 1.2 mL/min/g ± 0.5 [n = 29), compared with 1.3 mL/min/g ± 0.3 obtained with tracer microspheres in the same tissue specimens at the same time. The results represent a combination of T1-weighted first-pass imaging, intravascular relaxation agents, and a spatially distributed perfusion model to obtain absolute regional myocardial blood flow and volume.
PMCID: PMC4037321  PMID: 7766986
Contrast agent, blood pool; Contrast enhancement; Coronary vessels, diseases, 54.76; Heart, flow dynamics; Heart, MR, 51.12143; Model, mathematical; Myocardium, blood supply, 511.12143; Myocardium, MR, 511.12143; Perfusion studies
5.  Multiparametric MRI of Prostate Cancer: An Update on State-of-the-Art Techniques and Their Performance in Detecting and Localizing Prostate Cancer 
Magnetic resonance (MR) examinations of men with prostate cancer are most commonly performed for detecting, characterizing, and staging the extent of disease to best determine diagnostic or treatment strategies, which range from biopsy guidance to active surveillance to radical prostatectomy. Given both the exam's importance to individual treatment plans and the time constraints present for its operation at most institutions, it is essential to perform the study effectively and efficiently. This article reviews the most commonly employed modern techniques for prostate cancer MR examinations, exploring the relevant signal characteristics from the different methods discussed and relating them to intrinsic prostate tissue properties. Also, a review of recent articles using these methods to enhance clinical interpretation and assess clinical performance is provided.
PMCID: PMC3741996  PMID: 23606141
prostate cancer; multiparametric MRI; T2-weighted imaging; diffusion-weighted imaging; dynamic contrast-enhanced imaging; magnetic resonance spectroscopy
6.  Multi-system repeatability and reproducibility of apparent diffusion coefficient measurement using an ice-water phantom 
Quantitative quality control procedures were sought to evaluate technical variability in multi-center measurements of the diffusion coefficient of water as a prerequisite to use of the biomarker apparent diffusion coefficient (ADC) in multi-center clinical trials.
Materials and Methods
A uniform data acquisition protocol was developed and shared with 18 participating test sites along with a temperature-controlled diffusion phantom delivered to each site. Usable diffusion weighted imaging data of ice water at 5 b-values were collected on 35 clinical MRI systems from 3 vendors at 2 field strengths (1.5 and 3T) and analyzed at a central processing site.
Standard deviation of bore-center ADCs measured across 35 scanners was <2%; error range: −2% to +5% from literature value. Day-to-day repeatability of the measurements was within 4.5%. Intra-exam repeatability at the phantom center was within 1%. Excluding one outlier, inter-site reproducibility of ADC at magnet isocenter was within 3%, though variability increased for off-center measurements. Significant (>10%) vendor-specific and system-specific spatial non-uniformity ADC bias was detected for the off-center measurement that was consistent with gradient non-linearity.
Standardization of DWI protocol has improved reproducibility of ADC measurements and allowed identifying spatial ADC non-uniformity as a source of error in multi-site clinical studies.
PMCID: PMC3548033  PMID: 23023785
diffusion; MRI; phantom; ice-water; quality control; gradient non-linearity
7.  In vivo Validation of 4D Flow MRI for Assessing the Hemodynamics of Portal Hypertension 
to implement and validate in vivo radial 4D flow MRI for quantification of blood flow in the hepatic arterial, portal venous and splanchnic vasculature of healthy volunteers and patients with portal hypertension.
Methods & Materials
17 patients with portal hypertension and 7 subjects with no liver disease were included in this HIPAA-compliant and IRB-approved study. Exams were conducted at 3T using a 32-channel body coil with large volumetric coverage and 1.4mm isotropic true spatial resolution. Using post-processing software, cut-planes orthogonal to vessels were used to quantify flow (L/min) in the hepatic and splanchnic vasculature.
Flow quantification was successful in all cases. Portal vein and supra-celiac aorta flow demonstrated high variability among patients. Measurements were validated indirectly using internal consistency at three different locations within the portal vein (error=4.2±3.9%) and conservation of mass at the portal confluence (error=5.9±2.5%) and portal bifurcation (error=5.8±3.1%).
This work demonstrates the feasibility of radial 4D flow MRI to quantify flow in the hepatic and splanchnic vasculature. Flow results agreed well with data reported in the literature, and conservation of mass provided indirect validation of flow quantification. Flow in patients with portal hypertensions demonstrated high variability with patterns and magnitude consistent with the hyperdynamic state that commonly occurs in portal hypertension.
PMCID: PMC4000737  PMID: 23148034
4D Flow MRI; Hepatic Hemodynamics; Portal Hypertension
8.  1H Magnetic Resonance Spectroscopy of Neurodegeneration in a Mouse Model of Niemann-Pick Type C1 Disease 
To evaluate brain metabolite levels as in vivo indicators of disease progression in a widely studied mouse model of Niemann-Pick type C1 (NPC1) disease with quantitative 1H Magnetic Resonance Spectroscopy (MRS).
Materials and Methods
Single voxel MRS experiments were carried out in vivo in a mouse model of NPC1 disease and in control mice in two brain regions (central and posterior) at two time points (presymptomatic and end stage) to examine changes in metabolite levels in NPC1 disease. Concentrations of nine metabolites were quantified by fitting a simulated basis set of metabolite signals to the acquired spectra.
The only differences found in brain metabolite levels between NPC1 disease model and control mice were increased myo-inositol and decreased taurine in the posterior region of the brain at the end stage of the disease. Metabolite changes reported in past clinical MRS studies of NPC disease were not found in the current study of the mouse model.
The 1H spectra obtained from NPC1 mice and control mice were very similar, even at end stages of the disease. Although differences in two metabolites associated with neurodegenerative diseases were found and could inform future studies of the disease model, it appears that MRS in this mouse model of NPC1 disease does not have the sensitivity desired for a biomarker.
PMCID: PMC3652275  PMID: 23165972
Niemann-Pick type C1 disease; NPC1; MRS; neurodegeneration; taurine; myo-inositol
9.  Recovery of chemical Estimates by Field Inhomogeneity Neighborhood Error Detection (REFINED): Fat/Water Separation at 7T 
To reduce swaps in fat-water separation methods, a particular issue on 7T small animal scanners due to field inhomogeneity, using image postprocessing innovations that detect and correct errors in the B0 field map.
Materials and Methods
Fat-water decompositions and B0 field maps were computed for images of mice acquired on a 7T Bruker BioSpec scanner, using a computationally efficient method for solving the Markov Random Field formulation of the multi-point Dixon model. The B0 field maps were processed with a novel hole-filling method, based on edge strength between regions, and a novel k-means method, based on field-map intensities, which were iteratively applied to automatically detect and reinitialize error regions in the B0 field maps. Errors were manually assessed in the B0 field maps and chemical parameter maps both before and after error correction.
Partial swaps were found in 6% of images when processed with FLAWLESS. After REFINED correction, only 0.7% of images contained partial swaps, resulting in an 88% decrease in error rate. Complete swaps were not problematic.
Ex post facto error correction is a viable supplement to a priori techniques for producing globally smooth B0 field maps, without partial swaps. With our processing pipeline, it is possible to process image volumes rapidly, robustly, and almost automatically.
PMCID: PMC3535522  PMID: 23023815
REFINED; B0 field map estimation; fat-water imaging; Dixon imaging; fat-water swap; Markov Random Field; Iterated Conditional Modes
10.  Multiphasic Contrast-Enhanced MRI: Single-Slice Versus Volumetric Quantification of Tumor Enhancement for the Assessment of Renal Clear-Cell Carcinoma Fuhrman Grade 
To assess the association between clear-cell carcinoma pathology grade at nephrectomy and magnetic resonance imaging (MRI) tumor enhancement.
Materials and Methods
The Institutional Review Board approved this retrospective study and waived the informed consent requirement. In all, 32 patients underwent multiphase contrast-enhanced MRI prior to nephrectomy. MRI tumor enhancement was measured using two approaches: 1) the most enhancing portion of the tumor on a single slice and 2) volumetric analysis of enhancement in the entire tumor. Associations between pathological grade, tumor size, and enhancement were evaluated using the Kruskal–Wallis test and generalized logistic regression models.
No significant association between pathology grade and enhancement was found when measurements were made on a single slice. When measured in the entire tumor, significant associations were found between higher pathology grades and lower mean, median, top 10%, top 25%, and top 50% tumor enhancement (P < 0.001–0.002). On multivariate analysis the association between grade and enhancement remained significant (P = 0.041–0.043), but tumor size did not make an additional contribution beyond tumor enhancement alone in differentiating between tumor grades.
There is significant association between tumor grade and enhancement, but only when measured in the entire tumor and not on the most enhancing portion on a single slice.
PMCID: PMC3989993  PMID: 23152173
renal cell carcinoma; clear cell carcinoma; magnetic resonance imaging; genitourinary; oncology; aggressiveness
11.  Neonatal Neuroimaging Findings in Inborn Errors of Metabolism 
Individually, metabolic disorders are rare, but overall they account for a significant number of neonatal disorders affecting the central nervous system. The neonatal clinical manifestations of inborn errors of metabolism (IEMs) are characterized by nonspecific systemic symptoms that may mimic more common acute neonatal disorders like sepsis, severe heart insufficiency, or neonatal hypoxic-ischemic encephalopathy. Certain IEMs presenting in the neonatal period may also be complicated by sepsis and cardiomyopathy. Early diagnosis is mandatory to prevent death and permanent long-term neurological impairments. Although neuroimaging findings are rarely specific, they play a key role in suggesting the correct diagnosis, limiting the differential diagnosis, and may consequently allow early initiation of targeted metabolic and genetic laboratory investigations and treatment. Neuroimaging may be especially helpful to distinguish metabolic disorders from other more common causes of neonatal encephalopathy, as a newborn may present with an IEM prior to the availability of the newborn screening results. It is therefore important that neonatologists, pediatric neurologists, and pediatric neuroradiologists are familiar with the neuroimaging findings of metabolic disorders presenting in the neonatal time period.
PMCID: PMC4000315  PMID: 22566357
inborn errors of metabolism; neonates; neuroimaging; brain; MRI
12.  Registration of Dynamic Contrast-Enhanced MRI of the Common Carotid Artery Using a Fixed-Frame Template-Based Squared-Difference Method 
This study examines template-based squared-difference registration for motion correction in dynamic contrast-enhanced (DCE) MRI studies of the carotid artery wall and compares the results of fixed-frame template-based registration with a previously proposed consecutive-frame registration method.
Materials and Methods
Ten T1-weighted black-blood, turbo spin-echo DCE-MRI studies of the carotid artery wall were used to test template-based squared-difference registration. An intermediate image from each series was selected as the fixed-frame template for registration. Squared-difference minimization was used to align each image and template. Time-intensity curves generated from data aligned with template-based squared-difference registration were compared with gold standard curves created by drawing regions of interest on each image in the series. The results were also compared with unregistered data and data after consecutive-frame squared-difference registration.
An analysis of variance test of root mean-square error values between gold standard curve and curves from unregistered data and data registered with consecutive-frame and fixed-frame template-based methods was significant (P < 0.005) with template-based squared-difference registration producing curves that most closely matched the gold standard.
A fixed-frame template-based squared-difference registration method was proposed and validated for alignment of DCE-MRI of carotid arteries.
PMCID: PMC3998102  PMID: 24123809
registration; template-matching; vascular DCE-MRI
13.  Quantitative Analysis of T2-correction in Single-Voxel Magnetic Resonance Spectroscopy of Hepatic Lipid Fraction 
To investigate the accuracy and reproducibility of hepatic lipid measurements using 1H MRS with T2 relaxation correction, in comparison to measurements without correction.
Materials and Methods
Experiments were conducted in phantoms of varying lipid and iron-induced susceptibility to simulate fatty liver with variable T2. Single-voxel 1H MRS was conducted with multiple TE values, and lipid content (lipid%) was determined at each TE to assess accuracy and TE dependency. Concurrently, T2 and equilibrium values of water and lipid were determined separately, and T2 effects on the lipid% were corrected. A similar procedure was conducted in 12 human subjects to determine susceptibility effects on water and lipid MRS signals and lipid%. Multiple measurements were used to test reproducibility.
The use of T2-correction was found to be more accurate than uncorrected lipid% in phantom samples (<10% error). Uncorrected lipid% error increased with increasing TE (>20% when TE >24ms) and with increasing susceptibility effect. In humans, while measurement repeatability was high for both corrected and uncorrected MRS, uncorrected lipid% was sensitive to acquisition TE, with 83.6% of all measurements significantly different than T2-corrected measures (p<0.05).
Separate T2-correction of water and lipid 1H MRS signals provides more accurate and consistent measurements of lipid%, in comparison to uncorrected estimations.
PMCID: PMC3985419  PMID: 19243059
Spectroscopy; Hepatic Lipid; T2-correction
14.  A Computer-Controlled, MR-compatible Foot-Pedal Device to Study Dynamics of the Muscle Tendon Complex under Isometric, Concentric and Eccentric Contractions 
To design a computer-controlled, MR compatible foot pedal device that allows in vivo mapping of changes in morphology and in strain of different musculoskeletal components of the lower leg under passive, isometric, concentric and eccentric contractions.
Materials and Methods
A programmable servo-motor in the control room pumped hydraulic fluid to rotate a foot-pedal inside the magnet. Towards validating the performance of the device, six subjects were imaged with gated velocity-encoded phase-contrast (VE-PC) imaging to investigate dynamics of muscle and aponeurotic structures.
Artifact-free VE-PC imaging clearly delineated different muscle compartments by differences in distribution of mechanical strains. High repeatability of contraction cycles allowed establishing that fascicles lengthened 6.1% more during passive compared to eccentric contractions. Aponeurosis separation during passive (range between three locations: −2.6~1.3 mm) and active (range: −2.4 ~1.6 mm) contractions were similar but significantly different from concentric (range: −0.9~3.3 mm), with proximal and distal regions showing mostly negative values for the first two modes, but positive for the last.
The device was sufficiently robust and artifact-free to accurately assess, using VE-PC imaging, physiologically important structure and dynamics of the musculo-tendon complex.
PMCID: PMC3984931  PMID: 22392816
Magnetic Resonance Imaging (MRI) compatible device; Foot Pedal; Cine Velocity Encoded Phase Contrast MRI; Muscle dynamics; Muscle Fiber Architecture
15.  Measuring the longitudinal relaxation time of GABA in vivo at 3T 
To measure the in vivo longitudinal relaxation time T1 of GABA at 3T.
Materials and Methods
J-difference edited single-voxel magnetic resonance spectroscopy was used to isolate GABA signals. An increased echo time (80 ms) acquisition was used, accommodating the longer, more selective editing pulses required for symmetric editing-based suppression of co-edited macromolecular signal. Acquiring edited GABA measurements at a range of relaxation times in ten healthy participants, a saturation-recovery equation was used to model the integrated data.
The longitudinal relaxation time of GABA was measured as T1,GABA = 1.31 ± 0.16 s.
The method described has been successfully applied to measure the T1 of GABA in vivo at 3T.
PMCID: PMC3531569  PMID: 23001644
GABA; MRS; 3T; MEGA-PRESS; T1 relaxation; macromolecules
16.  Aortic Pulse Wave Velocity Measurements with Undersampled 4D Flow-Sensitive MRI: Comparison to 2D and Algorithm Determination 
To compare pulse wave velocity (PWV) measurements obtained from radially undersampled 4D phase-contrast MRI (PC-MRI) with 2DPC measurements and to evaluate four PWV algorithms.
PWV was computed from radially undersampled 3-dimensional, 3-directionally velocity-encoded PC-MRI acquisitions performed on a 3T MR scanner in 18 volunteers. High temporal resolution 2DPC scans serving as a reference standard were available in 14 volunteers. Four PWV algorithms were tested: time-to-upstroke (TTU), time-to-peak (TTP), time-to-foot (TTF), and cross-correlation (XCorr). Bland-Altman analysis was used to determine inter- and intraobserver reproducibility and to compare differences between algorithms. Differences in age and PWV measurements were analyzed with Student’s t-tests. The variability of age-corrected data was assessed with a Brown-Forsythe ANOVA test.
2D (4.6–5.3m/s) and 4D (3.8–4.8m/s) PWV results were in agreement with previously reported values in healthy subjects. Of the four PWV algorithms, the TTU, TTF, and XCorr algorithms gave similar and reliable results. Average biases of +0.30m/s and −0.01m/s were determined for intra- and interobserver variability, respectively. The Brown-Forsythe test revealed that no differences in variability could be found between 2D and 4D PWV measurements.
4D PC-MRI with radial undersampling provides reliable and reproducible measurements of PWV. TTU, TTF, and XCorr were the preferred PWV algorithms.
PMCID: PMC3566322  PMID: 23124585
4D PC MRI; phase contrast; pulse wave velocity; radial undersampling
17.  Automated unsupervised multi-parametric classification of adipose tissue depots in skeletal muscle 
To introduce and validate an automated unsupervised multi-parametric method for segmentation of the subcutaneous fat and muscle regions in order to determine subcutaneous adipose tissue (SAT) and intermuscular adipose tissue (IMAT) areas based on data from a quantitative chemical shift-based water-fat separation approach.
Materials and Methods
Unsupervised standard k-means clustering was employed to define sets of similar features (k = 2) within the whole multi-modal image after the water-fat separation. The automated image processing chain was composed of three primary stages including tissue, muscle and bone region segmentation. The algorithm was applied on calf and thigh datasets to compute SAT and IMAT areas and was compared to a manual segmentation.
The IMAT area using the automatic segmentation had excellent agreement with the IMAT area using the manual segmentation for all the cases in the thigh (R2: 0.96) and for cases with up to moderate IMAT area in the calf (R2: 0.92). The group with the highest grade of muscle fat infiltration in the calf had the highest error in the inner SAT contour calculation.
The proposed multi-parametric segmentation approach combined with quantitative water-fat imaging provides an accurate and reliable method for an automated calculation of the SAT and IMAT areas reducing considerably the total post-processing time.
PMCID: PMC3573225  PMID: 23097409
magnetic resonance imaging (MRI); water-fat imaging; subcutaneous adipose tissue (SAT); intermuscular adipose tissue (IMAT); fat quantification; multi-parametric clustering
18.  Pulmonary Vein Morphology by Free-Breathing Whole Heart Magnetic Resonance Imaging at 3T vs. Breathhold Multi-Detector Computed Tomography 
This study compares pulmonary vein and left atrial anatomy using 3D free-breathing whole-heart magnetic resonance imaging (MR) at 3T and multi-detector computed tomography (MDCT).
Materials and Methods
Thirty three subjects (19 male, age 49±12 years) underwent free-breathing 3T MR and contrast-enhanced MDCT during inspiratory breath hold. Pulmonary vein parameters (ostial areas, diameters, angles) were measured.
All pulmonary veins and anomalies were identified by 3T MR and by MDCT. The right-sided pulmonary veins were directed more posteriorly, the right superior pulmonary vein more inferiorly, and the right inferior pulmonary vein more superiorly by 3T MR when compared with MDCT. The cross-sectional area, perimeters and minimum diameters of right-sided pulmonary vein ostia were significantly larger by MR, as were the maximum diameters of right and left inferior pulmonary veins. There were no significant differences between techniques in distance to first pulmonary vein branch.
Pulmonary vein measurements demonstrated significant differences in angulations and dimensions when 3T MR is compared with MDCT. These differences likely represent hemodynamic and respiratory variation during free-breathing with MR versus breath-holding with MDCT. MR imaging at 3T during free-breathing offers an alternate method to define pulmonary vein and left atrial anatomy without exposure to radiation.
PMCID: PMC3584192  PMID: 23172711
magnetic resonance imaging; multidetector computed tomography; atrium; pulmonary vein; vessels
19.  Proton MRS in Mild Cognitive Impairment 
Mild cognitive impairment (MCI) is a clinical syndrome operationalized for early diagnosis and treatment of Alzheimer’s disease (AD). Many individuals with MCI are at the prodromal stage of AD or other dementia. Various quantitative MR techniques that measure the anatomic, biochemical, microstructural, functional, and blood-flow changes are being evaluated as possible surrogate measures for early diagnosis and disease progression in AD. The pathology underlying MCI heterogenous, dominated by AD, cerebrovascular disease, Lewy body disease, or a mixture of these pathologies in community-based autopsy cohorts. Proton MRS metabolite markers may help identify and track etiologies that typically underlie MCI in the elderly. The role of proton MRS will especially be critical for pathophysiological processes for which a reliable biomarker does not exist such as glial and microglial activation in neurodegenerative dementia.
PMCID: PMC3609038  PMID: 23526756
Mild cognitive impairment; magnetic resonance spectroscopy; dementia; Alzheimer’s disease
20.  Effectiveness of MR Angiography for the Primary Diagnosis of Acute Pulmonary Embolism: Clinical Outcomes at 3 Months and 1 Year 
To determine the effectiveness of MR angiography for pulmonary embolism (MRA-PE) in symptomatic patients.
Materials and Methods
We retrospectively reviewed all patients whom were evaluated for possible pulmonary embolism (PE) using MRA-PE. A 3-month and 1-year from MRA-PE electronic medical record (EMR) review was performed. Evidence for venous thromboembolism (VTE) (or death from PE) within the year of follow-up was the outcome surrogate for this study.
There were 190 MRA-PE exams performed with 97.4% (185/190) of diagnostic quality. There were 148 patients (120 F: 28 M) that had both a diagnostic MRA-PE exam and 1 complete year of EMR follow-up. There were 167 patients (137 F: 30 M) with 3 months or greater follow-up. We found 83% (139/167) and 81% (120/148) MRA-PE exams negative for PE at 3 months and 1 year, respectively. Positive exams for PE were seen in 14% (23/167). During the 1-year follow-up period, five patients (false negative) were diagnosed with DVT (5/148 = 3.4 %), and one of these patients also experienced a non–life-threatening PE. The negative predictive value (NPV) for MRA-PE was 97% (92–99; 95% CI) at 3 months and 96% (90–98; 95% CI) with 1 year of follow-up.
The NPV of MRA-PE, when used for the primary diagnosis of pulmonary embolism in symptomatic patients, were found to be similar to the published values for CTA-PE. In addition, the technical success rate and safety of MRA-PE were excellent.
PMCID: PMC3970266  PMID: 23553735
pulmonary embolism; magnetic resonance angiography; effectiveness; outcomes analysis; negative predictive value
21.  Evaluation of Quantitative Magnetic Resonance Imaging, Biochemical and Mechanical Properties of Trypsin-Treated Intervertebral Discs Under Physiological Compression Loading 
To investigate the influence of targeted trypsin digestion and 16 hours compression loading on MR parameters and the mechanical and biochemical properties of bovine disc segments.
Materials and Methods
Twenty-two 3-disc bovine coccygeal segments underwent compression loading for 16 hours after the nucleus pulposus (NP) of each disc was injected with a solution of trypsin or buffer. The properties of the NP and annulus fibrosus (AF) tissues of each disc were analyzed by quantitative MRI, biochemical tests, and confined compression tests.
Loading had a significant effect on the MR properties (T1, T2, T1ρ, MTR, ADC) of both the NP and AF tissues. Loading had a greater effect on the MR parameters and biochemical composition of the NP than trypsin. In contrast, trypsin had a larger effect on the mechanical properties. Our data also indicated that localized trypsin injection predominantly affected the NP. T1ρ was sensitive to loading and correlated with the water content of the NP and AF but not with their proteoglycan content.
Our studies indicate that physiological loading is an important parameter to consider and that T1ρ contributes new information in efforts to develop quantitative MRI as a noninvasive diagnostic tool to detect changes in early disc degeneration.
PMCID: PMC3963138  PMID: 18219615
quantitative MRI; intervertebral disc; T1ρ; biomechanics; loading
22.  A Dedicated Automated Injection System for Dynamic Contrast-Enhanced MRI Experiments in Mice 
To develop a reproducible small-animal dynamic contrast-enhanced (DCE) MRI set-up for mice through which volumes <100μL can be accurately and safely injected and to test this set-up via DCE measurements in resting muscle and tumor tissue.
Materials and Methods
The contrast agent (CA) injection system comprised 2 MR-compatible syringe pumps placed 50cm from the 7T magnet bore where the fringe field is about 40mT. Microbore tubing and T-connector, close to the injection site, minimized dead volume (<10μL). For DCE-MRI measurements in 8 CB-17 SCID mice with 1500–2500mm3 large orthotopic neuroblastoma, a bolus of 10-fold-diluted Gd-DTPA CA solution (0.1mmol/kg) was delivered (5μL/s), followed by a 50μL saline flush. Retro-orbital injections were given instead of tail vein injections, since the peripheral vasculature was reduced because of large tumor burden.
The CA injection was successful in 19 of 24 experiments. Optical assessment showed minimal dispersion of ink-colored CA bolus. Mean (±SD) pharmacokinetic parameters retrieved from DCE-MRI examinations in resting muscle (Ktrans=0.038±0.025min−1, kep=0.66±0.48min−1, ve=0.060±0.014, vp=0.033±0.021) and tumor (Ktrans=0.082±0.071min−1, kep=0.82±0.80min−1, ve=0.121±0.075, vp=0.093±0.051) agreed with those reported previously.
We successfully designed and implemented a DCE-MRI set-up system with short injection lines and low dead volume. The system can be used at any field strength with the syringe pumps placed at a sufficiently low fringe field (<40mT).
PMCID: PMC3529995  PMID: 23001593
mice; injection system; dynamic contrast enhanced MRI; arterial input function; retro-orbital
23.  Adipose Tissue MRI for Quantitative Measurement of Central Obesity 
To validate adipose tissue magnetic resonance imaging (atMRI) for rapid, quantitative volumetry of visceral adipose tissue (VAT) and total adipose tissue (TAT).
Materials and Methods
Data was acquired on normal adults and clinically-overweight girls with IRB approval/parental consent using sagittal 6-echo 3D-SPGR (26-sec single-breath-hold) at 3T. Fat-fraction images were reconstructed with quantitative corrections, permitting measurement of a physiologically-based fat-fraction threshold in normals to identify adipose tissue, for automated measurement of TAT and semi-automated measurement of VAT. TAT accuracy was validated using oil phantoms and in vivo TAT/VAT measurements validated with manual segmentation. Group comparisons were performed between normals and overweight girls using TAT, VAT, VAT-TAT-ratio (VTR), body-mass-index (BMI), waist circumference, and waist-hip-ratio (WHR).
Oil phantom measurements were highly accurate (< 3% error). The measured adipose fat-fraction threshold was 96% ± 2%. VAT and TAT correlated strongly to manual segmentation (normals r2 ≥ 0.96, overweight girls r2 ≥ 0.99). VAT segmentation required 30 ± 11 minutes/subject (14 ± 5 sec/slice) using atMRI, versus 216 ± 73 minutes/subject (99 ± 31 sec/slice) manually. Group discrimination was significant using WHR (p < 0.001) and VTR (p = 0.004).
The atMRI technique permits rapid, accurate measurements of TAT, VAT and VTR.
PMCID: PMC3543762  PMID: 23055365
adipose tissue; body mass index; metabolic syndrome; central obesity
24.  R2* Estimation using “In-Phase” Echoes in the Presence of Fat: The Effects of Complex Spectrum of Fat 
To investigate R2* mapping robustness in the presence of fat using in-phase echoes, without and with spectral modeling of fat (single-peak and multi-peak models, respectively), using varying numbers of echoes.
Materials and Methods
Data from 88 volunteers (men/women: 52/36, ages: 55.4±12.2) were randomly chosen according to MRI liver fat-fraction (%), and classified into 6 fat-fraction groups (1: 20 cases, 0–<10%; 2: 20 cases, 10–<20%; 3: 20 cases, 20–<30%; 4: 20 cases, 30–<40%; 5: 8 cases >40% liver fat; 6: subcutaneous fat from all cases). R2* maps obtained from 5 in-phase echoes (echo times: 4.8–23.8ms) were retrospectively reconstructed using single-peak and multi-peak fat modeling. R2* maps were also calculated using different numbers (2–5) of echoes.
Multi-peak fat corrected R2* mapping is feasible from in-phase echoes, with noise performance comparable to single-peak R2* when using ≥4 echoes. Single-peak R2* showed poor robustness to varying echo time combinations in the presence of fat, where using few echoes resulted in large errors. These errors can be reduced using more echoes, or fully corrected using multi-peak fat modeling. The mean R2* increased significantly with increasing fat-fraction when using single-peak R2* for any TE combination (p<0.001), but did not vary when using multi-peak R2* for any TE combination (p≥0.158).
R2* mapping uncorrected for spectral complexity of fat contains protocol and fat-dependent errors (lack of robustness) in tissues with high fat content. Accounting for complex fat spectrum improves robustness and accuracy of signal fitting, with modest noise performance loss.
PMCID: PMC3578028  PMID: 23055408
R2*; liver; in-phase; fat; multi-peak
25.  Temporal dynamics of lactate concentration in the human brain during acute inspiratory hypoxia 
To demonstrate the feasibility of measuring the temporal dynamics of cerebral lactate concentration and examine these dynamics in human subjects using MRS during hypoxia.
A respiratory protocol consisting of 10 min baseline normoxia, 20 min inspiratory hypoxia and ending with 10 min normoxic recovery was used, throughout which lactate-edited MRS was performed. This was repeated four times in three subjects. A separate session was performed to measure blood lactate. Impulse response functions using end-tidal oxygen and blood lactate as system inputs and cerebral lactate as the system output were examined to describe the dynamics of the cerebral lactate response to a hypoxic challenge.
The average lactate increase was 20%±15% during the last half of the hypoxic challenge. Significant changes in cerebral lactate concentration were observed after 400s. The average relative increase in blood lactate was 188%±95%. The temporal dynamics of cerebral lactate concentration was reproducibly demonstrated with 200s time bins of MRS data (coefficient of variation 0.063±0.035 between time bins in normoxia). The across subject coefficient of variation was 0.333.
The methods for measuring the dynamics of the cerebral lactate response developed here would be useful to further investigate the brain’s response to hypoxia.
PMCID: PMC3578150  PMID: 23197421
lactate; cerebral lactate; magnetic resonance spectroscopy; hypoxia; neuroimaging; impulse response function

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