Maged Goubran

The spectrum of structural and functional imaging abnormalities in temporal lobe epilepsy

Although most temporal lobe epilepsy (TLE) patients show marked hippocampal sclerosis (HS) upon pathological examination, 40% present with no significant cell loss but gliotic changes only. To evaluate effects of hippocampal pathology on brain structure and functional networks, we aimed at dissociating multimodal magnetic resonance imaging (MRI) characteristics in patients with HS (TLE‐HS) and those with gliosis only (TLE‐G).

Direct Visualization and Mapping of the Spatial Course of Fiber Tracts at Microscopic Resolution in the Human Hippocampus

Abstract While hippocampal connectivity is essential to normal memory function, our knowledge of human hippocampal circuitry is largely inferred from animal studies. Using polarized light microscopy at 1.3 &mgr;m resolution, we have directly visualized the 3D course of key medial temporal pathways in 3 ex vivo human hemispheres and 2 ex vivo vervet monkey hemispheres. The multiple components of the perforant path system were clearly identified: Superficial sheets of fibers emanating from the entorhinal cortex project to the presubiculum and parasubiculum, intermixed transverse and longitudinal angular bundle fibers perforate the subiculum and then project to the cornu ammonis (CA) fields and dentate molecular layer, and a significant alvear component runs from the angular bundle to the CA fields. From the hilus, mossy fibers localize to regions of high kainate receptor density, and the endfolial pathway, mostly investigated in humans, merges with the Schaffer collaterals. This work defines human hippocampal pathways underlying mnemonic function at an unprecedented resolution.

Seven-Tesla MRI and neuroimaging biomarkers for Alzheimer’s disease

The goal of this paper was to review the effectiveness of using 7-T MRI to study neuroimaging biomarkers for Alzheimers disease (AD). The authors reviewed the literature for articles published to date on the use of 7-T MRI to study AD. Thus far, there are 3 neuroimaging biomarkers for AD that have been studied using 7-T MRI in AD tissue: 1) neuroanatomical atrophy; 2) molecular characterization of hypointensities; and 3) microinfarcts. Seven-Tesla MRI has had mixed results when used to study the 3 aforementioned neuroimaging biomarkers for AD. First, in the detection of neuroanatomical atrophy, 7-T MRI has exciting potential. Historically, noninvasive imaging of neuroanatomical atrophy during AD has been limited by suboptimal resolution. However, now there is compelling evidence that the high resolution of 7-T MRI may help overcome this hurdle. Second, in detecting the characterization of hypointensities, 7-T MRI has had varied success. PET scans will most likely continue to lead in the noninvasive imaging of amyloid plaques; however, there is emerging evidence that 7-T MRI can accurately detect iron deposits within activated microglia, which may help shed light on the role of the immune system in AD pathogenesis. Finally, in the detection of microinfarcts, 7-T MRI may also play a promising role, which may help further elucidate the relationship between cerebrovascular health and AD progression.

The separate effects of lipids and proteins on brain MRI contrast revealed through tissue clearing

&NA; Despite the widespread use of magnetic resonance imaging (MRI) of the brain, the relative contribution of different biological components (e.g. lipids and proteins) to structural MRI contrasts (e.g., T1, T2, T2*, proton density, diffusion) remains incompletely understood. This limitation can undermine the interpretation of clinical MRI and hinder the development of new contrast mechanisms. Here, we determine the respective contribution of lipids and proteins to MRI contrast by removing lipids and preserving proteins in mouse brains using CLARITY. We monitor the temporal dynamics of tissue clearance via NMR spectroscopy, protein assays and optical emission spectroscopy. MRI of cleared brain tissue showed: 1) minimal contrast on standard MRI sequences; 2) increased relaxation times; and 3) diffusion rates close to free water. We conclude that lipids, present in myelin and membranes, are a dominant source of MRI contrast in brain tissue. HighlightsCharacterized lipid removal and protein retention of CLARITY tissue clearing method.Evidence that lipids are more significant contributor to MRI contrast than proteins.MRI of cleared tissue had increased relaxation times and increased diffusion rates.

Transcranial MRI-guided high-intensity focused ultrasound for treatment of essential tremor: A pilot study on the correlation between lesion size, lesion location, thermal dose, and clinical outcome

Transcranial MR‐guided high‐intensity focused ultrasound (tcMRgFUS) is a promising noninvasive method to treat medication‐refractory essential tremor.

Assessment of PET & ASL metabolism in the hippocampal subfields of MCI and AD using simultaneous PET-MR.

Alzheimer’s disease (AD) has been reported to show decreased metabolic activity in the hippocampus using FDG PET-MR. Histological data suggests that the hippocampal subfields are selectively affected in AD. Given the simultaneous imaging nature of integrated PET-MR scanners and the multimodal capabilities of PET-MR, our purpose here is to assess FDG activity, as well as ASL perfusion in the subfields of MCI and AD patients. 10 consecutive subjects were recruited for this study 3 MCI, 3 AD patients and 4 age-matched controls. The scanning was performed on a simultaneous 3T PET/MR scanner. To delineate the hippocampal subfields, automatic segmentation of hippocampal subfields (ASHS) was employed. Static FDG-PET series were reconstructed for analysis at 45-75 min for all subjects. All imaging sequences were automatically registered to the oblique coronal T2-weighted images (segmentation space). PET standardized uptake values (SUV) in the hippocampal subfields were normalized by the pons. FDG PET metabolism was reduced significantly in AD, as well as MCI patients as compared to controls, with the highest effect demonstrated in the CA3/DG and CA1/2 (p = 0.047, subfields. Patients (MCI and AD combined) had decreased metabolism as compared to controls in CA1/2 and significantly smaller volumes the Subiculum. When assessing CBF across groups, a significant decrease in CBF was found in the Subiculum. Our preliminary results demonstrate that PET-MRI may potentially be a sensitive biomarker and tool for early diagnosis of AD. They also confirm the importance of assessing metabolic and structural changes of neurodegenerative diseases at the subfield level.

Correlation between arterial spin labeling MRI and dynamic FDG on PET-MR in Alzheimer’s disease and non-Alzhiemer’s disease patients

Regional hypoperfusion on Arterial Spin Labeling (ASL) MRI and corresponding regions of hypometabolism on FDG PET have been reported in Alzheimer’s Disease (AD). To our knowledge these correlations have not been studied under simultaneous acquisition. The purpose of this study is to investigate the correlation of ASL with FDG PET under simultaneous acquisition on PET-MR and to explore this correlation as a possible biomarker for AD. Dynamic FDG and ASL imaging was performed using a simultaneous TOF-enabled PET-MR scanner in 7 subjects without AD and 3 subjects with AD. Average age was 68±5 years. Automated atlas-based segmentation was performed using T2 MRI using the Talairach atlas. Quantitative analysis of ASL and FDG (delayed 45-75 minute scan) was performed in five regions using the pons as a reference region for both perfusion and metabolism. Statistical analyses included Spearman’s correlation and student’s t-test. Significant correlation of relative perfusion and metabolism was found in two of the five brain regions including the putamen (p = 0.018) and the hippocampus (p = 0.031). In addition, there was significant difference between the relative perfusion and metabolism of the thalamus (p = 0.04). No difference was seen between the AD and non-AD groups. Simultaneous PET-MR demonstrates a positive correlation of perfusion of ASL with metabolism on FDG PET in the hippocampus and putamen. The putamen correlation has previously been reported in the literature on a non-simultaneous ASL and FDG imaging. The thalamus was noted to have a difference in the relative perfusion and metabolism representing a perfusion-metabolism mismatch. Future studies should explore the correlation in additional brain regions and the meaning of perfusion-metabolism mismatches as potential imaging biomarkers for patients with and without AD.

Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor

Purpose To evaluate the use of diffusion magnetic resonance imaging (MRI) tractography for neurosurgical guidance of transcranial MRI-guided focused ultrasound (tcMRgFUS) thalamotomy for essential tremor (ET). Materials and methods Eight patients with medication-refractory ET were treated with tcMRgFUS targeting the ventral intermediate nucleus (Vim) of the thalamus contralateral to their dominant hand. Diffusion and structural MRI data and clinical evaluations were acquired pre-treatment and post-treatment. To identify the optimal target location, tractography was performed on pre-treatment diffusion MRI data between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus. The tractography-identified locations were compared to the lesion location delineated on 1u202fyear post-treatment T2-weighted MR image. Their overlap was correlated with the clinical outcomes measured by the percentage change of the Clinical Rating Scale for Tremor scores acquired pre-treatment, as well as 1u202fmonth, 3u202fmonths, 6u202fmonths and 1u202fyear post-treatment. Results The probabilistic tractography was consistent from subject-to-subject and followed the expected anatomy of the thalamocortical radiation and the dentatothalamic tract. Higher overlap between the tractography-identified location and the tcMRgFUS treatment-induced lesion highly correlated with better treatment outcome (ru202f=u202f−0.929, −0.75, −0.643, pu202f=u202f0.00675, 0.0663, 0.139 for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus, respectively, at 1u202fyear post-treatment). The correlation for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex is the highest for all time points (ru202f=u202f−0.719, −0.976, −0.707, −0.929, pu202f=u202f0.0519, 0.000397, 0.0595, 0.00675 at 1u202fmonth, 3u202fmonths, 6u202fmonths and 1u202fyear post-treatment, respectively). Conclusion Our data support the use of diffusion tractography as a complementary approach to current targeting methods for tcMRgFUS thalamotomy.

Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI)

Amplified magnetic resonance imaging (aMRI) was recently introduced as a new brain motion detection and visualization method. The original aMRI approach used a video‐processing algorithm, Eulerian video magnification (EVM), to amplify cardio‐ballistic motion in retrospectively cardiac‐gated MRI data. Here, we strive to improve aMRI by incorporating a phase‐based motion amplification algorithm.

FEASIBILITY OF USING X-RAY FLUORESCENCE IMAGING AND ABSORPTION SPECTROSCOPY TO EVALUATE IRON DISTRIBUTION AND OXIDATIVE STATE IN THE ALZHEIMER'S DISEASE HIPPOCAMPUS

(NanoSIMS) in a combined approach we term SILK-SIMS. Results: 1) In human AD brain, the incorporation of tracer into plaques in a participant with clinical stage AD dementia suggests that plaques can be dynamic with activity over days even in later stages of disease. 2) Tracer enrichment was highly variable and asymmetric with both quiescent and active nanometer sub-regions of tracer incorporation. 3) Neurons are hyper-metabolic cells compared to surrounding neuropil. We will demonstrate whether disturbed neuronal metabolism (a proxy for function) may be indicative of declining neuronal health and whether this is correlated with the presence of tau aggregates. Conclusions: SILK-SIMS studies will provide invaluable information on plaque dynamics and neuronal health, and tau aggregation in the normal and diseased brain. These studies will offer new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development.