Faculty Bibliography

There is a need for accurate quantitative non-invasive biomarkers to monitor myelin pathology in vivo and distinguish myelin changes from other pathological features including inflammation and axonal loss. Conventional MRI metrics such as T2, magnetization transfer ratio and radial diffusivity have proven sensitivity but not specificity. In highly coherent white matter bundles, compartment-specific white matter tract integrity (WMTI) metrics can be directly derived from the diffusion and kurtosis tensors: axonal water fraction, intra-axonal diffusivity, and extra-axonal radial and axial diffusivities. We evaluate the potential of WMTI to quantify demyelination by monitoring the effects of both acute (6weeks) and chronic (12weeks) cuprizone intoxication and subsequent recovery in the mouse corpus callosum, and compare its performance with that of conventional metrics (T2, magnetization transfer, and DTI parameters). The changes observed in vivo correlated with those obtained from quantitative electron microscopy image analysis. A 6-week intoxication produced a significant decrease in axonal water fraction (p<0.001), with only mild changes in extra-axonal radial diffusivity, consistent with patchy demyelination, while a 12-week intoxication caused a more marked decrease in extra-axonal radial diffusivity (p=0.0135), consistent with more severe demyelination and clearance of the extra-axonal space. Results thus revealed increased specificity of the axonal water fraction and extra-axonal radial diffusivity parameters to different degrees and patterns of demyelination. The specificities of these parameters were corroborated by their respective correlations with microstructural features: the axonal water fraction correlated significantly with the electron microscopy derived total axonal water fraction (rho=0.66; p=0.0014) but not with the g-ratio, while the extra-axonal radial diffusivity correlated with the g-ratio (rho=0.48; p=0.0342) but not with the electron microscopy derived axonal water fraction. These parameters represent promising candidates as clinically feasible biomarkers of demyelination and remyelination in the white matter.

OBJECTIVE: This study evaluates use of an abbreviated magnetic resonance imaging protocol with T2-weighted imaging in detecting biopsy-proven unifocal breast cancer. MATERIALS AND METHODS: This is an institutional review board approved retrospective study of patients with biopsy-proven unifocal breast cancer (88% invasive; 12% in situ) undergoing magnetic resonance imaging. In three separate sessions, three breast imagers evaluated (1) T1-weighted non-contrast, post-contrast and post-contrast subtracted images, (2) T1-weighted images with clinical history and prior imaging, and (3) T1-weighted images and T2-weighted images with clinical history and prior imaging. Protocols were compared for cancer detection, reading time and lesion conspicuity. An independent breast radiologist retrospectively analyzed initial enhancement ratio of cancers and retrospectively reviewed lesion morphology and final pathology. RESULTS: All 107 cancers were identified at first protocol by at least one reader; five cancers were missed by either one or two readers. One cancer was missed by one reader at protocols two and three. Mean percentage detection for protocol one was 97.8%; protocol two, 99.4%, protocol three, 99.4%. T2-weighted images did not alter cancer detection but increased lesion conspicuity for 2/3 readers. 3/5 missed lesions were low grade cancers. Initial enhancement ratio was positively associated with increasing tumor grade (p=0.031) and pathology (p=0.002). Reader interpretation time decreased and lesion conspicuity increased as initial enhancement ratio increased. CONCLUSION: Abbreviated magnetic resonance imaging has high rate of detection for known breast cancer and short interpretation time. T2 weighted imaging increased lesion conspicuity without altering detection rate. Initial enhancement ratio correlated with invasive disease and tumor grade.

BACKGROUND: To evaluate the influence of temporal sparsity regularization and radial undersampling on compressed sensing reconstruction of dynamic contrast-enhanced (DCE) MRI, using the iterative Golden-angle RAdial Sparse Parallel (iGRASP) MRI technique in the setting of breast cancer evaluation. METHODS: DCE-MRI examinations of the breast (n = 7) were conducted using iGRASP at 3 Tesla. Images were reconstructed with five different radial undersampling schemes corresponding to temporal resolutions between 2 and 13.4 s/frame and with four different weights for temporal sparsity regularization (lambda = 0.1, 0.5, 2, and 6 times of noise level). Image similarity to time-averaged reference images was assessed by two breast radiologists and using quantitative metrics. Temporal similarity was measured in terms of wash-in slope and contrast kinetic model parameters. RESULTS: iGRASP images reconstructed with lambda = 2 and 5.1 s/frame had significantly (P < 0.05) higher similarity to time-averaged reference images than the images with other reconstruction parameters (mutual information (MI) >5%), in agreement with the assessment of two breast radiologists. Higher undersampling (temporal resolution < 5.1 s/frame) required stronger temporal sparsity regularization (lambda >/= 2) to remove streaking aliasing artifacts (MI > 23% between lambda = 2 and 0.5). The difference between the kinetic-model transfer rates of benign and malignant groups decreased as temporal resolution decreased (82% between 2 and 13.4 s/frame). CONCLUSION: This study demonstrates objective spatial and temporal similarity measures can be used to assess the influence of sparsity constraint and undersampling in compressed sensing DCE-MRI and also shows that the iGRASP method provides the flexibility of optimizing these reconstruction parameters in the postprocessing stage using the same acquired data. J. Magn. Reson. Imaging 2015.

OBJECTIVES: We aimed to investigate the effect of T2* correction on estimation of kinetic parameters from T1-weighted dynamic contrast enhanced (DCE) MRI data when a reference-tissue arterial input function (AIF) is used. MATERIALS AND METHODS: DCE-MRI data were acquired from seven mice with 4T1 mouse mammary tumors using a double gradient echo sequence at 7 T. The AIF was estimated from a region of interest in the muscle. The extended Tofts model was used to estimate pharmacokinetic parameters in the enhancing part of the tumor, with and without T2* correction of the lesion and AIF. The parameters estimated with T2* correction of both the AIF and lesion time-intensity curve were assumed to be the reference standard. RESULTS: For the whole population, there was significant difference (p < 0.05) in transfer constant (K(trans)) between T2* corrected and not corrected methods, but not in interstitial volume fraction (ve). Individually, no significant differences were found in K(trans) and ve of four and six tumors, respectively, between the T2* corrected and not corrected methods. In contrast, K(trans) was significantly underestimated, if the T2* correction was not used, in other tumors for which the median K(trans) was larger than 0.4 min(-1). CONCLUSION: T2* effect on tumors with high K(trans) may not be negligible in kinetic model analysis, even if AIF is estimated from reference tissue where the concentration of contrast agent is relatively low.

OBJECTIVE: To measure background parenchymal enhancement (BPE) and compare with other contrast enhancement values and diffusion-weighted MRI parameters in healthy and cancerous breast tissue at the clinical level. MATERIALS AND METHODS: This HIPAA-compliant, IRB approved retrospective study enrolled 77 patients (38 patients with breast cancer - mean age 51.8+/-10.0 years; 39 high-risk patients for screening evaluation - mean age 46.3+/-11.7 years), who underwent contrast-enhanced 3T breast MRI. Contrast enhanced MRI and diffusion-weighted imaging were performed to quantify BPE, lesion contrast enhancement, and apparent diffusion coefficient (ADC) metrics in fibroglandular tissue (FGT) and lesions. RESULTS: BPE did not correlate with ADC values. Mean BPE for the lesion-bearing patients was higher (43.9%) compared to that of the high-risk screening patients (28.3%, p=0.004). Significant correlation (r=0.37, p<0.05) was found between BPE and lesion contrast enhancement. CONCLUSION: No significant association was observed between parenchymal or lesion enhancement with conventional apparent diffusion metrics, suggesting that proliferative processes are not co-regulated in cancerous and parenchymal tissue.

PURPOSE: To compare fitting methods and sampling strategies, including the implementation of an optimized b-value selection for improved estimation of intravoxel incoherent motion (IVIM) parameters in breast cancer. METHODS: Fourteen patients (age, 48.4 +/- 14.27 years) with cancerous lesions underwent 3 Tesla breast MRI examination for a HIPAA-compliant, institutional review board approved diffusion MR study. IVIM biomarkers were calculated using "free" versus "segmented" fitting for conventional or optimized (repetitions of key b-values) b-value selection. Monte Carlo simulations were performed over a range of IVIM parameters to evaluate methods of analysis. Relative bias values, relative error, and coefficients of variation (CV) were obtained for assessment of methods. Statistical paired t-tests were used for comparison of experimental mean values and errors from each fitting and sampling method. RESULTS: Comparison of the different analysis/sampling methods in simulations and experiments showed that the "segmented" analysis and the optimized method have higher precision and accuracy, in general, compared with "free" fitting of conventional sampling when considering all parameters. Regarding relative bias, IVIM parameters fp and Dt differed significantly between "segmented" and "free" fitting methods. CONCLUSION: IVIM analysis may improve using optimized selection and "segmented" analysis, potentially enabling better differentiation of breast cancer subtypes and monitoring of treatment. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

PURPOSE: To quantitatively evaluate temporal blurring of dynamic contrast-enhanced MRI data generated using a k-space weighted image contrast (KWIC) image reconstruction technique with golden-angle view-ordering. METHODS: K-space data were simulated using golden-angle view-ordering and reconstructed using a KWIC algorithm with a Fibonacci number of views enforced for each annulus in k-space. Temporal blurring was evaluated by comparing pharmacokinetic model parameters estimated from the simulated data with the true values. Diagnostic accuracy was quantified using receiver operator characteristic curves (ROC) and the area under the ROC curves (AUC). RESULTS: Estimation errors of pharmacokinetic model parameters were dependent on the true curve type and the lesion size. For 10mm benign and malignant lesions, estimated AUC values using the true and estimate AIFs were consistent with the true AUC value. For 5mm benign and 20mm malignant lesions, estimated AUC values using the true and estimated AIFs were 0.906+/-0.020 and 0.905+/-0.021, respectively, as compared with the true AUC value of 0.896. CONCLUSIONS: Although the investigated reconstruction algorithm does impose errors in pharmacokinetic model parameter estimation, they are not expected to significantly impact clinical studies of diagnostic accuracy.

BACKGROUND AND PURPOSE: Whole brain radiation therapy (WBRT) may cause cognitive and neuropsychological impairment and hence objective assessment of adverse effects of radiation may be valuable to plan therapy. The purpose of our study was to determine the potential of echo planar spectroscopic imaging (EPSI) and diffusion tensor imaging (DTI) in detecting subacute radiation induced injury to the normal brain. MATERIALS AND METHODS: Four patients with brain metastases and three patients with lung cancer underwent cranial irradiation. These patients were subjected to 3D-EPSI and DTI at two time points (pre-radiation, and 1 month post-irradiation). Parametric maps of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), mean diffusivity (MD), and fractional anisotropy (FA) were generated and co-registered to post-contrast T1-weighted images. Normal appearing gray-matter and white-matter regions were compared between the two time points to assess sub-acute effects of radiation using independent sample t-tests. RESULTS: Significantly increased MD (P = .02), Cho/Cr (P = .02) and a trend towards a decrease in NAA/Cr (P = .06) was observed from the hippocampus. Significant decrease in FA (P = .02) from the centrum-semiovale and a significant increase in MD (P = .04) and Cho/Cr (P = .02) from genu of corpus-callosum was also observed. CONCLUSIONS: Our preliminary findings suggest that 3D-EPSI and DTI may provide quantitative measures of radiation induced injury to the normal brain.

PURPOSE: To develop a fast and flexible free-breathing dynamic volumetric MRI technique, iterative Golden-angle RAdial Sparse Parallel MRI (iGRASP), that combines compressed sensing, parallel imaging, and golden-angle radial sampling. METHODS: Radial k-space data are acquired continuously using the golden-angle scheme and sorted into time series by grouping an arbitrary number of consecutive spokes into temporal frames. An iterative reconstruction procedure is then performed on the undersampled time series where joint multicoil sparsity is enforced by applying a total-variation constraint along the temporal dimension. Required coil-sensitivity profiles are obtained from the time-averaged data. RESULTS: iGRASP achieved higher acceleration capability than either parallel imaging or coil-by-coil compressed sensing alone. It enabled dynamic volumetric imaging with high spatial and temporal resolution for various clinical applications, including free-breathing dynamic contrast-enhanced imaging in the abdomen of both adult and pediatric patients, and in the breast and neck of adult patients. CONCLUSION: The high performance and flexibility provided by iGRASP can improve clinical studies that require robustness to motion and simultaneous high spatial and temporal resolution. Magn Reson Med, 2013. (c) 2013 Wiley Periodicals, Inc.

Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. PAPERCLIP: