Faculty Bibliography

Besides amyloid deposition, white matter (WM) changes are involved in the early pathogenesis of Alzheimer's Disease (AD), including inflammation, demyelination and axonal loss. Using simultaneous PET and MRI, we investigated differences in WM microstructural integrity, measured with Diffusion Kurtosis Imaging (DKI), with respect to beta amyloid (Aa) deposition as measured with18F-Florbetapir PET. DKI is a clinically feasible diffusion MRI method that extends beyond Diffusion Tensor Imaging and probes non-Gaussian diffusion properties of nervous tissue, and allows for quantifying the microstructural index for the axonal water fraction (AWF), a specific marker for axonal degeneration and demyelination. Methods: 34 subjects were scanned on a 3T integrated PET-MRI system (Siemens Biograph mMR, VB20). 18FFlorbetapir (9 mCi, Eli Lilly) was injected intravenously and a static 20-minute PET image was reconstructed starting at 40 min post-injection using a UTE-based attenuation map. An anatomical MP-RAGE was acquired for cortical and sub-cortical segmentation using Freesurfer. Hippocampal volume was normalized to the estimated total intracranial volume. The standardized uptake values (SUV) in 5 cortical regions known for pathological uptake of Florbetapir (anterior and posterior cingulate, medial orbito-frontal, parietal and temporal), normalized to the cerebellum, yielded mean cortical relative SUV (SUVr). DKI provided parametric maps for the radial diffusivity (RD), radial kurtosis (RK), and the AWF. Using a lower and higher mean SUVr threshold of 1.0 and 1.1, age- and gender-controlled subjects were categorized into Aa negative (Aa-) (n = 13, 5 females, age = 69.8 +/- 5.1 yrs), Aa intermediate (Aai) (n = 13, 8 females, age = 68.9 +/- 4.8 yrs), or Aa positive (Aa+) (n = 8, 4 females, age = 70.6 +/- 5.3 yrs). Using Tract-Based Spatial Statistics (TBSS), skeletonized voxel-wise analysis was performed to identify areas of differences in the diffusion metrics while covarying for age. Separately, WM regions of interests (ROIs) were automatically segmented using atlas registration over which mean values were extracted. Analysis of covariance covarying for age was used to compare diffusion metrics and hippocampal volume among groups. Results: See figure. Results from both TBSS and ROI analysis demonstrated changes in the fornix and the genu of the corpus callosum. Between the Aa- and Aai groups, RD decreased while RK and AWF increased. Conversely, between the Aai and Aa+ groups, RD increased RD while RK and AWF decreased. A trend towards significantly higher hippocampal volume in the Aai group was observed. Conclusions: We report changes in RD, RK and AWF in opposite directions between Aa- and Aa~, and between Aa~ and Aa+, respectively, suggesting that different mechanisms affect the microstructure during different stages of AD. Early on, mechanisms including microglial activation may restrict diffusion, resulting in the observed decrease in RD and increase in RK and AWF. Later on, neurodegenerative effects such as demyelination and axonal loss may outweigh inflammation, resulting in the observed increase in RD and decrease in RK and AWF. [IMAGE PRESENTED]

BACKGROUND AND PURPOSE: Obtaining high-resolution brain MR imaging in patients with a previously implanted deep brain stimulator has been challenging and avoided by many centers due to safety concerns relating to implantable devices. We present our experience with a practical clinical protocol at 1.5T by using 2 magnet systems capable of achieving presurgical quality imaging in patients undergoing bilateral, staged deep brain stimulator insertion. MATERIALS AND METHODS: Protocol optimization was performed to minimize the specific absorption rate while providing image quality necessary for adequate surgical planning of the second electrode placement. We reviewed MR imaging studies performed with a minimal specific absorption rate protocol in patients with a deep brain stimulator in place at our institution between February 1, 2012, and August 1, 2015. Images were reviewed by a neuroradiologist and a functional neurosurgeon. Image quality was qualitatively graded, and the presence of artifacts was noted. RESULTS: Twenty-nine patients (22 with Parkinson disease, 6 with dystonia, 1 with essential tremor) were imaged with at least 1 neuromodulation implant in situ. All patients were imaged under general anesthesia. There were 25 subthalamic and 4 globus pallidus implants. Nineteen patients were preoperative for the second stage of bilateral deep brain stimulator placement; 10 patients had bilateral electrodes in situ and were being imaged for other neurologic indications, including lead positioning. No adverse events occurred during or after imaging. Mild device-related local susceptibility artifacts were present in all studies, but they were not judged to affect overall image quality. Minimal aliasing artifacts were seen in 7, and moderate motion, in 4 cases on T1WI only. All preoperative studies were adequate for guidance of a second deep brain stimulator placement. CONCLUSIONS: An optimized MR imaging protocol that minimizes the specific absorption rate can be used to safely obtain high-quality images in patients with previously implanted deep brain stimulators, and these images are adequate for surgical guidance.

BACKGROUND: There is substantial overlap between MRI of acute spinal cord lesions from neuromyelitis optica (NMO) and spinal cord infarct (SCI) in clinical practice. However, early differentiation is important since management approaches to minimize morbidity from NMO or SCI differ significantly. OBJECTIVE: To identify MRI features at initial presentation that may help to differentiate NMO acute myelitis from SCI. METHODS: 2 board-certified neuroradiologists, blinded to final diagnosis, retrospectively characterized MRI features at symptom onset for subjects with serologically-proven NMO (N=13) or SCI (N=11) from a single institution. Univariate and multivariate analyses were used to identify factors associated with NMO or SCI. RESULTS: SCI was more common in men and Caucasians, while NMO was more common in non-Caucasian women (P<0.05). MRI features associated with NMO acute myelitis (P<0.05) included location within 7-cm of cervicomedullary junction; lesion extending to pial surface; 'bright spotty lesions' on axial T2 MRI; and gadolinium enhancement. Patient's age, lesion length and cross-sectional area, cord expansion, and the "owl's eyes" sign did not differ between the two groups (P>0.05). CONCLUSION: Along with patient demographic characteristics, lesion features on MRI, including lesion location, extension to pial border and presence of 'bright spotty lesion' can help differentiate acute myelitis of NMO from SCI in the acute setting.

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.