Faculty Bibliography

Diffusion imaging of the spine has the potential to change clinical management, but is challenging due to the small size of the cord and susceptibility artifacts from adjacent structures. Reduced field-of-view (rFOV) diffusion can improve image quality by decreasing the echo train length. Over the past 2 years, we have acquired a rFOV diffusion sequence for MRI spine protocols on most inpatients and emergency room patients. We provide selected imaging diagnoses to illustrate the utility of including diffusion spine MRI in clinical practice. Our experiences support using diffusion MRI to improve diagnostic certainty and facilitate prompt treatment or clinical management.

Functional neurosurgery is a rapidly growing field with exciting future potential applications. This article describes currently used implanted electronic devices for neurologic stimulation and monitoring. The devices to be reviewed include invasive EEG electrodes, deep brain stimulator, motor cortex stimulator, responsive neurostimulation, osteo-integrated hearing aid, middle ear implant, cochlear implant, auditory brainstem implant, vagal nerve stimulator and spinal cord stimulator. Emphasis is placed on the normal components, function, positioning, potential complications and MRI safety of these devices. Understanding the motivations and appropriate use of these implantable devices is critical for clinical neuroradiologists to provide relevant imaging interpretation and protocols for patients and referring physicians.

BACKGROUND: Clinical orbital MRI protocols are routinely used to study the optic nerves and exclude compressive lesions, infarctions, or inflammation. However, the small caliber and divergent oblique orientations of the optic nerves make it challenging to characterize them well with conventional MRI, especially since adjacent air-filled bony structures distort the MRI signal and motion is a problem even in cooperative, healthy volunteers. EVIDENCE ACQUISITION: Over the past 3 years we have experimented with multiple novel MRI approaches and sequences to better characterize the optic nerves. The perfect MRI protocol would be quantitative and sensitive to subtle optic nerve pathologic changes, provide high spatial resolution, be rapidly acquired, and resistant to motion degradation. RESULTS: This review provides an update of recent MRI sequence innovations for the optic nerves being currently translated into clinical practice. Methods discussed include rapid MRI with compressed sensing or simultaneous multislice approaches, postprocessing techniques for quantitative T2 mapping or track density imaging, and multiple MRI sequences for measuring diffusion in the optic nerves. CONCLUSIONS: Recently-developed orbit-specific MRI coils, quantitative sequences, and rapid acquisition techniques can improve our future ability to study optic nerve pathologies noninvasively. As advanced MRI becomes more proficient at characterizing the optic nerves, its role in the clinical management of patients should increase.

Current consensus diagnostic criteria for multiple system atrophy (MSA) consider dementia a non-supporting feature, although cognitive impairment and even frank dementia are reported in clinical practice. Mini-Mental State Examination (MMSE) is a commonly used global cognitive scale, and in a previous study, we established an MSA-specific screening cut-off score <27 to identify cognitive impairment. Finally, MSA neuroimaging findings suggest the presence of structural alterations in patients with cognitive deficits, although the extent of the anatomical changes is unclear. The aim of our multicenter study is to better characterize anatomical changes associated with cognitive impairment in MSA and to further investigate cortical and subcortical structural differences versus healthy controls (HC). We examined retrospectively 72 probable MSA patients [50 with normal cognition (MSA-NC) and 22 cognitively impaired (MSA-CI) based on MMSE <27] and compared them to 36 HC using gray- and white-matter voxel-based morphometry and fully automated subcortical segmentation. Compared to HC, MSA patients showed widespread cortical (bilateral frontal, occipito-temporal, and parietal areas), subcortical, and white-matter alterations. However, MSA-CI showed only focal volume reduction in the left dorsolateral prefrontal cortex compared with MSA-NC. These results suggest only a marginal contribution of cortical pathology to cognitive deficits. We believe that cognitive dysfunction is driven by focal fronto-striatal degeneration in line with the concept of "subcortical cognitive impairment".

Palliative cervical cordotomy can be performed via percutaneous radiofrequency ablation of the lateral C1-2 spinothalamic tract. This rare procedure can be safe, effective, and advantageous in mitigating medically intractable unilateral extremity pain for selected patients with end-stage cancer. This report reviews the indications, techniques, risks, and potential benefits of cordotomy. We describe our recent experience treating 3 patients with CT-guided C1-2 cordotomy and provide the first characterization of spinal cord diffusion MR imaging changes associated with successful cordotomy.

PURPOSE: Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors. EXPERIMENTAL DESIGN: Here, we used 33 single cell-derived subclones generated from five clinical glioblastoma specimens for exploring intra- and inter-individual spectra of drug resistance profiles in vitro. In a personalized setting, we explored whether differences in pharmacological sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors. RESULTS: Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential anti-glioblastoma compounds. A more comprehensive intra-tumoral analysis revealed that stable genetic and phenotypic characteristics of co-existing subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naive parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacological profiles could be shown for establishing rational strategies for individualized secondary lines of treatment. CONCLUSIONS: Our data provide a previously unrecognized strategy for revealing functional consequences of intra-tumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma.

INTRODUCTION: Quantitative T2 mapping may provide an objective biomarker for occult nervous tissue pathology in relapsing-remitting multiple sclerosis (RRMS). We applied a novel echo modulation curve (EMC) algorithm to identify T2 changes in normal-appearing brain regions of subjects with RRMS (N = 27) compared to age-matched controls (N = 38). METHODS: The EMC algorithm uses Bloch simulations to model T2 decay curves in multi-spin-echo MRI sequences, independent of scanner, and scan-settings. T2 values were extracted from normal-appearing white and gray matter brain regions using both expert manual regions-of-interest and user-independent FreeSurfer segmentation. RESULTS: Compared to conventional exponential T2 modeling, EMC fitting provided more accurate estimations of T2 with less variance across scans, MRI systems, and healthy individuals. Thalamic T2 was increased 8.5% in RRMS subjects (p < 0.001) and could be used to discriminate RRMS from healthy controls well (AUC = 0.913). Manual segmentation detected both statistically significant increases (corpus callosum & temporal stem) and decreases (posterior limb internal capsule) in T2 associated with RRMS diagnosis (all p < 0.05). In healthy controls, we also observed statistically significant T2 differences for different white and gray matter structures. CONCLUSIONS: The EMC algorithm precisely characterizes T2 values, and is able to detect subtle T2 changes in normal-appearing brain regions of RRMS patients. These presumably capture both axon and myelin changes from inflammation and neurodegeneration. Further, T2 variations between different brain regions of healthy controls may correlate with distinct nervous tissue environments that differ from one another at a mesoscopic length-scale.