Faculty Bibliography

The purpose of this work was to carry out diffusion tensor imaging (DTI) at multiple diffusion times Td in skeletal muscle in normal subjects and chronic exertional compartment syndrome (CECS) patients and analyze the data with the random permeable barrier model (RPBM) for biophysical specificity. Using an institutional review board approved HIPAA-compliant protocol, seven patients with clinical suspicion of CECS and eight healthy volunteers underwent DTI of the calf muscle in a Siemens MAGNETOM Verio 3 T scanner at rest and after treadmill exertion at four different Td values. Radial diffusion values lambdarad were computed for each of seven different muscle compartments and analyzed with RPBM to produce estimates of free diffusivity D0 , fiber diameter a, and permeability kappa. Fiber diameter estimates were compared with measurements from literature autopsy reference for several compartments. Response factors (post/pre-exercise ratios) were computed and compared between normal controls and CECS patients using a mixed-model two-way analysis of variance. All subjects and muscle compartments showed nearly time-independent diffusion along and strongly time-dependent diffusion transverse to the muscle fibers. RPBM estimates of fiber diameter correlated well with corresponding autopsy reference. D0 showed significant (p < 0.05) increases with exercise for volunteers, and a increased significantly (p < 0.05) in volunteers. At the group level, response factors of all three parameters showed trends differentiating controls from CECS patients, with patients showing smaller diameter changes (p = 0.07), and larger permeability increases (p = 0.07) than controls. Time-dependent diffusion measurements combined with appropriate tissue modeling can provide enhanced microstructural specificity for in vivo tissue characterization. In CECS patients, our results suggest that high-pressure interfiber edema elevates free diffusion and restricts exercise-induced fiber dilation. Such specificity may be useful in differentiating CECS from other disorders or in predicting its response to either physical therapy or fasciotomy

PURPOSE: To develop a bilateral coil and fat suppressed T1-weighted sequence for 7 Tesla (T) breast MRI. MATERIALS AND METHODS: A dual-solenoid coil and three-dimensional (3D) T1w gradient echo sequence with B1 + insensitive fat suppression (FS) were developed. T1w FS image quality was characterized through image uniformity and fat-water contrast measurements in 11 subjects. Signal-to-noise ratio (SNR) and flip angle maps were acquired to assess the coil performance. Bilateral contrast-enhanced and unilateral high resolution (0.6 mm isotropic, 6.5 min acquisition time) imaging highlighted the 7T SNR advantage. RESULTS: Reliable and effective FS and high image quality was observed in all subjects at 7T, indicating that the custom coil and pulse sequence were insensitive to high-field obstacles such as variable tissue loading. 7T and 3T image uniformity was similar (P = 0.24), indicating adequate 7T B1 + uniformity. High 7T SNR and fat-water contrast enabled 0.6 mm isotropic imaging and visualization of a high level of fibroglandular tissue detail. CONCLUSION: 7T T1w FS bilateral breast imaging is feasible with a custom radiofrequency (RF) coil and pulse sequence. Similar image uniformity was achieved at 7T and 3T, despite different RF field behavior and variable coil-tissue interaction due to anatomic differences that might be expected to alter magnetic field patterns. J. Magn. Reson. Imaging 2013. (c) 2013 Wiley Periodicals, Inc.

Purpose: To review radiation dose exposure for patients undergoing IVC filter placement in order to infer quantitative guidelines for expected doses. To identify strategies for targeted dose reduction. Materials and Methods: Records of 230 consecutive cases of IVC filter placement in Interventional Radiology at a single university hospital between 1/4/12 and 6/7/13 were reviewed. Patients under age 18 and patients with variant anatomy (e.g. duplicated IVC) or caval thrombosis were excluded. Radiation dose (mGy) was recorded from the fluoroscopic detector system; access site and patient information were noted. Subset analyses were performed, including analysis before and after exclusion of outliers (more than two SD from the mean) and before and after exclusion of cases without contrast (no DSA). Patients were stratified by access site, BMI, age, and gender; correlation with dose was analyzed using Spearman rank correlation and Mann-Whitney tests. Four access site categories were used: Right internal jugular (RIJ), left internal jugular (LIJ), right common femoral (RCF), and Other. Results: Mean radiation dose in all subjects was 67.55 mGy, and after outliers and non-contrast cases were excluded, 51.35 mGy.Radiation dose was highest in cases when IVC filters were placed via the RIJ compared with LIJ, RCF, and other access sites. Radiation dose was significantly lower in cases with filters placed via RCF than in those with filters placed via RIJ (p=0.018). Conclusion: Analysis of radiation dose in a standardized procedure-IVC filter placement-provides valuable information on expected dose range and potential dose reduction strategies. Access via RIJ (vs. RCF) resulted in significantly higher dose, raising the question: should a standard access site for IVC filter placement be considered? Additionally, this model will be implemented to identify dose reduction strategies for other standard interventional procedures. (Table Presented)

OBJECTIVE: This study aimed at identifying the optimal threshold value to detect cartilage lesions with Standardized dGEMRIC at 3T and evaluate intra- and inter-observer repeatability. DESIGN: We retrospectively reviewed 20 hips in 20 patients. dGEMRIC maps were acquired at 3T along radial imaging planes of the hip and standardized to remove the effects of patient's age, sex and diffusion of gadolinium contrast. Two observers separately evaluated 84 Standardized dGEMRIC maps, both by visual inspection and using an average index for a region of interest in the acetabular cartilage. A radiologist evaluated the acetabular cartilage on morphologic MR images at exactly the same locations. Using intra-operative findings as reference, the optimal threshold to detect cartilage lesions with Standardized dGEMRIC was assessed and results were compared with the diagnostic performance of morphologic MRI. RESULTS: Using z < -2 as threshold and visual inspection of the color-adjusted maps, sensitivity, specificity and accuracy for Observer 1 and Observer 2, were 83%, 60% and 75%, and 69%, 70% and 69%, respectively. Overall performance was 52%, 67% and 58%, when using an average z for the acetabular cartilage, compared to 37%, 90% and 56% for morphologic assessment. The kappa coefficient was 0.76 and 0.68 for intra- and inter-observer repeatability, respectively, indicating substantial agreement. CONCLUSIONS: Standardized dGEMRIC at 3T is accurate in detecting cartilage damage and could improve preoperative assessment in FAI. As cartilage lesions in FAI are localized, visual inspection of the Standardized dGEMRIC maps is more accurate than an average z for the acetabular cartilage.

OBJECTIVE: To obtain quantitative neurometabolite measurements, specifically myoinositol (mI) and glutamate plus glutamine (Glx), markers of glial and neuronal excitation, in deep gray matter structures after mild traumatic brain injury (mTBI) using proton magnetic resonance spectroscopy (1H-MRS) and to compare these measurements against normal healthy control subjects. METHODS: This study approved by the institutional review board is Health Insurance Portability and Accountability Act compliant. T1-weighted MRI and multi-voxel 1H-MRS imaging were acquired at 3 tesla from 26 patients with mTBI an average of 22 days postinjury and from 13 age-matched healthy controls. Two-way analysis of variance was used to compare patients and controls for mean N-acetylaspartate, choline, creatine (Cr), Glx, and mI levels as well as the respective ratios to Cr within the caudate, globus pallidus, putamen, and thalamus. RESULTS: Quantitative putaminal mI was higher in patients with mTBI compared with controls (p = 0.02). Quantitative neurometabolite ratios of putaminal mI and Glx relative to Cr, mI/Cr, and Glx/Cr were also higher among patients with mTBI compared with controls (p = 0.01 and 0.02, respectively). No other differences in neurometabolite levels or ratios were observed in any other brain region evaluated. CONCLUSION: Increased putaminal mI, mI/Cr, and Glx/Cr in patients after mTBI compared with control subjects supports the notion of a complex glial and excitatory response to injury without concomitant neuronal loss, evidenced by preserved N-acetylaspartate levels in this region.

OBJECTIVE: To compare the image quality of contrast-enhanced abdominopelvic 3D fat-suppressed T1-weighted gradient-echo imaging with radial and conventional Cartesian k-space acquisition schemes in paediatric patients. METHODS: Seventy-three consecutive paediatric patients were imaged at 1.5 T with sequential contrast-enhanced T1-weighted Cartesian (VIBE) and radial gradient echo (GRE) acquisition schemes with matching parameters when possible. Cartesian VIBE was acquired as a breath-hold or as free breathing in patients who could not suspend respiration, followed by free-breathing radial GRE in all patients. Two paediatric radiologists blinded to the acquisition schemes evaluated multiple parameters of image quality on a five-point scale, with higher score indicating a more optimal examination. Lesion presence or absence, conspicuity and edge sharpness were also evaluated. Mixed-model analysis of variance was performed to compare radial GRE and Cartesian VIBE. RESULTS: Radial GRE had significantly (all P < 0.001) higher scores for overall image quality, hepatic edge sharpness, hepatic vessel clarity and respiratory motion robustness than Cartesian VIBE. More lesions were detected on radial GRE by both readers than on Cartesian VIBE, with significantly higher scores for lesion conspicuity and edge sharpness (all P < 0.001). CONCLUSION: Radial GRE has better image quality and lesion conspicuity than conventional Cartesian VIBE in paediatric patients undergoing contrast-enhanced abdominopelvic MRI. KEY POINTS: * Numerous techniques are required to provide optimal MR images in paediatric patients. * Radial free-breathing contrast-enhanced acquisition demonstrated excellent image quality. * Image quality and lesion conspicuity were better with radial than Cartesian acquisition. * More lesions were detected on contrast-enhanced radial than on Cartesian acquisition. * Radial GRE can be used for performing abdominopelvic MRI in paediatric patients.

BACKGROUND: Invariant natural killer T (iNKT) cells are CD1d-restricted T cells, which respond rapidly to antigen recognition and promote development of anti-tumor immunity in many tumor models. Surprisingly, we previously found that mice deficient in iNKT cells developed spontaneous CD8(+) T cells responses partially effective at inhibiting metastases in mice bearing the 4T1 mammary carcinoma, and showed a markedly improved response to treatment with local radiotherapy and anti-CTLA-4 antibody compared to wild type (WT) mice. METHODS: To understand the mechanisms of the immunosuppressive function of iNKT cells, dendritic cells (DCs) were analyzed by immunohistochemistry and flow cytometry in WT and iNKT-deficient (iNKT(-/-)) mice. The effects of antibody-mediated blockade of CD1d on DC number and phenotype, priming of anti-tumor T cells, and tumor response to treatment with local radiotherapy and anti-CTLA-4 antibody were evaluated. To determine if the improved response to treatment in the absence of iNKT cells was independent from the immunotherapy employed, 4T1-tumor bearing WT and iNKT(-/-) mice were treated with local radiotherapy in combination with antibody-mediated CD137 co-stimulation. RESULTS: DCs in 4T1 tumors and tumor-draining lymph nodes but not distant lymph nodes were significantly reduced in WT mice compared to iNKT(-/-) mice (p < 0.05), suggesting the selective elimination of DCs cross-presenting tumor-associated antigens by iNKT cells. Consistently, priming of T cells to a tumor-specific CD8 T cell epitope in mice treated with radiotherapy and anti-CTLA-4 or anti-CD137 was markedly enhanced in iNKT(-/-) compared to WT mice. CD1d blockade restored the number of DC in WT mice, improved T cell priming in draining lymph nodes and significantly enhanced response to treatment. CONCLUSIONS: Here we describe a novel mechanism of tumor immune escape mediated by iNKT cells that limit priming of anti-tumor T cells by controlling DC in tumors and draining lymph nodes. These results have important implications for the design of immunotherapies targeting iNKT cells.

Microstructural white matter deficits in Autism Spectrum Disorders (ASD) have been suggested by both histological findings and Diffusion Tensor Imaging (DTI) studies, which show reduced fractional anisotropy (FA) and increased mean diffusivity (MD). However, imaging reports are generally not consistent across studies and the underlying physiological causes of the reported differences in FA and MD remain poorly understood. In this study, we sought to further characterize white matter deficits in ASD by employing an advanced diffusion imaging method, the Diffusional Kurtosis Imaging (DKI), and a two-compartment diffusion model of white matter. This model differentially describes intra- and extra-axonal white matter compartments using Axonal Water Fraction (faxon ) a measure reflecting axonal caliber and density, and compartment-specific diffusivity measures. Diagnostic utility of these measures and associations with processing speed performance were also examined. Comparative studies were conducted in 16 young male adults with High Functioning Autism (HFA) and 17 typically developing control participants (TDC). Significantly decreased faxon was observed in HFA compared to the control group in most of the major white matter tracts, including the corpus callosum, cortico-spinal tracts, and superior longitudinal, inferior longitudinal and inferior fronto-occipital fasciculi. Intra-axonal diffusivity (Daxon ) was also found to be reduced in some of these regions. Decreased axial extra-axonal diffusivity (ADextra ) was noted in the genu of the corpus callosum. Reduced processing speed significantly correlated with decreased faxon and Daxon in several tracts. faxon of the left cortico-spinal tract and superior longitudinal fasciculi showed good accuracy in discriminating the HFA and TDC groups. In conclusion, these findings suggest altered axonal microstructure in young adults with HFA which is associated with reduced processing speed. Compartment-specific diffusion metrics appear to improve specificity and sensitivity to white matter deficits in this population.

BACKGROUND AND OBJECTIVE: To examine whether clinically benign multiple sclerosis patients (BMS) show similar losses of their global N-acetylaspartate (NAA) neuronal marker relative to more clinically disabled patients of similar disease duration. METHODS: The whole-brain NAA concentration (WBNAA) was acquired with whole-head non-localizing proton MR spectroscopy. Fractional brain parenchymal volume (fBPV), T2 and T1 lesion loads, were obtained from the MRI in: (i) 24 BMS patients: 23.1+/-7.2 years disease duration, median Expanded Disability Status Scale (EDSS) score of 2.0 (range: 0-3); (ii) 26 non-benign MS patients (non-BMS), 24.5+/-7.4 years disease duration, median EDSS of 4.0 (range: 3.5-6.5); (iii) 15 healthy controls. RESULTS: Controls' 12.4+/-2.3mM WBNAA was significantly higher than the BMS's and non-BMS's 10.5+/-2.4 and 9.9+/-2.1mM (both p<0.02), but the difference between the patients' groups was not (p>0.4). Likewise, the controls' 81.2+/-4.5% fBPV exceeded the BMS and non-BMS's 77.0+/-5.8% and 76.3+/-8.6% (p<0.03), which were also not different from one another (p>0.7). BMS patients' T1-hypointense lesion load, 2.1+/-2.2cm(3), was not significantly different than the non-BMS's 4.1+/-5.4cm(3) (p>0.08) and T2-hyperintense loads: 6.0+/-5.7cm(3) and 8.7+/-7.8cm(3), were also not different (p>0.1). CONCLUSIONS: WBNAA differentiates normal controls from MS patients but does not distinguish BMS from more disabled MS patients of similar disease duration. Nevertheless, all MS patients who remain RR for 15+ years suffered WBNAA loss similar to the average RR MS population at fourfold shorter disease duration suggesting relative global neuronal sparing or leveling-off of the neurodegeneration rate.

PURPOSE: To evaluate the performance of diffusion tensor imaging (DTI) in the evaluation of chronic exertional compartment syndrome (CECS) as compared to T(2) -weighted (T2w) imaging. MATERIALS AND METHODS: Using an Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol, spectral adiabatic inversion recovery (SPAIR) T2w imaging and stimulated echo DTI were applied to eight healthy volunteers and 14 suspected CECS patients before and after exertion. Longitudinal and transverse diffusion eigenvalues, mean diffusivity (MD), and fractional anisotropy (FA) were measured in seven calf muscle compartments, which in patients were classified by their response on T2w: normal (<20% change), and CECS (>20% change). Mixed model analysis of variance compared subject groups and compartments in terms of response factors (post/pre-exercise ratios) of DTI parameters. RESULTS: All diffusivities significantly increased (P < 0.0001) and FA decreased (P = 0.0014) with exercise. Longitudinal diffusion responses were significantly smaller than transversal diffusion responses (P < 0.0001). Nineteen of 98 patient compartments were classified as CECS on T2w. MD increased by 3.8 +/- 3.4% (volunteer), 7.4 +/- 4.2% (normal), and 9.1 +/- 7.0% (CECS) with exercise. CONCLUSION: DTI shows promise as an ancillary imaging method in the diagnosis and understanding of the pathophysiology in CECS. Future studies may explore its utility in predicting response to treatment. J. Magn. Reson. Imaging 2013;. (c) 2013 Wiley Periodicals, Inc.