Faculty Bibliography

Simultaneous PET/MR of the brain is a promising new technology for characterizing patients with suspected cognitive impairment or epilepsy. Unlike CT though, MR signal intensities do not provide a direct correlate to PET photon attenuation correction (AC) and inaccurate radiotracer standard uptake value (SUV) estimation could limit future PET/MR clinical applications. We tested a novel AC method that supplements standard Dixon-based tissue segmentation with a superimposed model-based bone compartment. METHODS: We directly compared SUV estimation for MR-based AC methods to reference CT AC in 16 patients undergoing same-day, single 18FDG dose PET/CT and PET/MR for suspected neurodegeneration. Three Dixon-based MR AC methods were compared to

Two new 3T MR imaging contrast methods, track density imaging and echo modulation curve T2 mapping, were combined with simultaneous multisection acquisition to reveal exquisite anatomic detail at 7 canonical levels of the brain stem. Compared with conventional MR imaging contrasts, many individual brain stem tracts and nuclear groups were directly visualized for the first time at 3T. This new approach is clinically practical and feasible (total scan time = 20 minutes), allowing better brain stem anatomic localization and characterization.

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.

Objectives PET/MR may be used in the evaluation of cognitively impaired patients. There are known quantitative differences between PET images obtained on PET/MR scanners when reconstructed with Dixon-MR, CT-based or atlas-based attenuation correction (AC) maps. This study seeks to assess the impact, if any, of these three-different AC methods on the blinded visual interpretation of regional hypometabolism in patients with cognitive impairment. Methods Forty-five minutes following injection of 10 mCi of FDG, 15 patients with cognitive impairment underwent brain PET/CT. PET/MR scanning with a 10 minute PET acquisition and Dixon MR imaging was subsequently performed on a Siemens Biograph mMR scanner under an IRB-approved protocol, at approximately two hours post-injection. A manufacturer-provided non-product offline reconstruction tool was used to reconstruct PET data obtained from PET/MR with AC based on the patient's own CT images, a Dixon-MR derived AC map and an atlas-based AC map that combined Dixon-MR with a segmentation of bony skull structures. Two nuclear medicine physicians blindly scored brain regions (frontal, temporal, parietal, occipital, precuneus) as normal versus hypometabolic using 2D and 3D images generated by MIM software. Abnormal regions were scored as mild, moderate, or severely hypometabolic (score of 0, 1, 2 or 3 respectively). The hypometabolism scores obtained using the different methods of AC were compared and reader agreement assessed. All statistical tests were conducted at the two-sided 5% significance level using SAS 9.3 (SAS Institute, Cary, NC). Results Regional hypometabolism versus normal metabolism was correctly classified (accuracy) for 150 regions in 15 patients by two readers on atlas- and Dixon-based AC map PET reconstructions (versus CT reference AC) for 94% (90 - 96% c.i.) and 93% (89 - 96% c.i.) of all regions. The averaged sensitivity/specificity for detection of any regional hypometabolism was 95%/94% and 90%/91% for atlas-based and Dixon-based AC maps, respectively, compared to the reference standard CT images. The mean absolute error of regional hypometabolism scores for atlas- and Dixon-based PET reconstructions (versus CT) was 0.25 +/- 0.44 and 0.21 +/- 0.42 . There were no statistically significant differences between the visual assessments. Intra-reader agreement for detection of regional hypometabolism was high, with similar outcome assessments when using atlas- and Dixon-corrected PET data in 93% and 93% of scored regions, respectively. The simple kappa coefficient to assess reader agreement in terms of hypometabolism versus normal regions was 0.82 for atlas- and 0.84 for Dixon-based AC. The weighted kappa coefficient to assess reader agreement in terms of the hypometabolism score was 0.75 for atlas- and 0.77 for Dixon-AC. Conclusions Despite the more accurate FDG SUV quantification with CT-based and atlas-based attenuation correction in brain PET/MR compared to Dixon AC, there were no measureable differences between the three AC methods with respect to visual identification of regional hypometabolism in the evaluation of cognitively impaired patients

PURPOSE: Development of a quantitative transverse relaxation time (T2 )-mapping platform that operates at clinically feasible timescales by employing advanced image reconstruction of radially undersampled multi spin-echo (MSE) datasets. METHODS: Data was acquired on phantom and in vivo at 3 Tesla using MSE protocols employing radial k-space sampling trajectories. In order to overcome the nontrivial spin evolution associated with MSE protocols, a numerical signal model was precalculated based on Bloch simulations of the actual pulse-sequence scheme used in the acquisition process. This signal model was subsequently incorporated into an iterative model-based image reconstruction process, producing T2 and proton-density maps. RESULTS: T2 maps of phantom and in vivo brain were successfully constructed, closely matching values produced by a single spin-echo reference scan. High-resolution mapping was also performed for the spinal cord in vivo, differentiating the underlying gray/white matter morphology. CONCLUSION: The presented MSE data-processing framework offers reliable mapping of T2 relaxation values in a approximately 5-minute timescale, free of user- and scanner-dependent variations. The use of radial k-space sampling provides further advantages in the form of high immunity to irregular physiological motion, as well as enhanced spatial resolutions, owing to its inherent ability to perform alias-free limited field-of-view imaging. Magn Reson Med, 2015. (c) 2015 Wiley Periodicals, Inc.

A 32-year-old female with relapsing-remitting multiple sclerosis (MS) presented with severe new onset ataxia and diplopia. MRI showed a new inflammatory MS lesion that involved the right dorsal pons and extended into the adjacent superior cerebellar peduncle. The patient improved with aggressive immunotherapy; however, repeat MRI 3 months later revealed a new non-enhancing lesion in the left inferior medullary olive. The differential diagnosis for this new lesion included an MS lesion vs hypertrophic olivary degeneration, with infarct or neoplasm as the less likely considerations. We used track density imaging, which provides unprecedented anatomic details based on probabilistic tractography streamlines, to demonstrate apparent changes in the integrity of the dentato-rubro-olivary pathway (Guillain-Mollaret triangle) that were consistent with the diagnosis of hypertrophic olivary degeneration from the antecedent MS lesion involving the right superior cerebellar peduncle. Further medical therapy was avoided, and follow-up MRI 1 year later showed interval involution of the left olivary lesion. This case demonstrates the potential clinical utility of using track density imaging to detect lesion-induced alterations in brainstem connectivity and characterize neurodegeneration in patients.