Faculty Bibliography

Combining magnetic resonance imaging (MRI) with 2-deoxy-2-F-fluoro-D-glucose positron emission tomography (FDG-PET) data improve the imaging accuracy for detection of Alzheimer disease and related dementias. Integrated FDG-PET-MRI is a recent technical innovation that allows both imaging modalities to be obtained simultaneously from individual patients with cognitive impairment. This report describes the practical benefits and challenges of using integrated FDG-PET-MRI to support the clinical diagnosis of various dementias. Over the past 7 years, we have performed integrated FDG-PET-MRI on >1500 patients with possible cognitive impairment or dementia. The FDG-PET and MRI protocols are the same as current conventions, but are obtained simultaneously over 25 minutes. An additional Dixon MRI sequence with superimposed bone atlas is used to calculate PET attenuation correction. A single radiologist interprets all imaging data and generates 1 report. The most common positive finding is concordant temporoparietal volume loss and FDG hypometabolism that suggests increased risk for underlying Alzheimer disease. Lobar-specific atrophy and FDG hypometabolism patterns that may be subtle, asymmetric, and focal also are more easily recognized using combined FDG-PET and MRI, thereby improving detection of other neurodegeneration conditions such as primary progressive aphasias and frontotemporal degeneration. Integrated PET-MRI has many practical benefits to individual patients, referrers, and interpreting radiologists. The integrated PET-MRI system requires several modifications to standard imaging center workflows, and requires training individual radiologists to interpret both modalities in conjunction. Reading MRI and FDG-PET together increases imaging diagnostic yield for individual patients; however, both modalities have limitations in specificity.

BACKGROUND:Intramedullary spinal cord neoplasms (ISCN) pose significant management challenges. Advances in magnetic resonance imaging (MRI) (such as diffusion tensor imaging, DTI) have been utilized to determine the infiltrative nature and resectability of ISCN. However, this has not been applied to intraoperative decision making. OBJECTIVE:To present a case series of 2 patients with ISCN, the first to combine use of DTI, pre- and intraoperative 3-dimensional (3D) virtual reality imaging, and microscope integrated navigation with heads-up display. METHODS:Two patients who underwent surgery for ISCN were included. DTI images were obtained and 3D images were created using Surgical Theater (Surgical Theater SRP, Version 7.4.0, Cleveland, Ohio). Fiducials were used to achieve accurate surface registration to C4. Navigation confirmed the levels of laminectomy necessary. The microscope was integrated with Brainlab (Brainlab AG Version 3.0.5, Feldkirchen, Germany) and the tumor projected in the heads-up display. Surgical Theater was integrated with Brainlab to allow for real time evaluation of the 3D tractography. RESULTS:Case 1: All tracts were pushed away from the tumor, suggesting it was not infiltrative. Surgical Theater and Brainlab assisted in confirming midline despite the abnormal swelling of the cord so the myelotomy could be performed. The heads-up display outline demonstrated excellent correlation to the tumor. Gross total resection was achieved. Diagnosis of ependymoma was confirmed. Case 2: Some tracts were going through the tumor itself, suggesting an infiltrative process. Surgical Theater and Brainlab again allowed for confirmation of the midline raphe. Near total resection of the enhancing portion was achieved. Diagnosis of glioblastoma was confirmed. CONCLUSION/CONCLUSIONS:This is a proof of concept application where multi-modal imaging technology was utilized for safest maximal ISCN resection.

At very low diffusion weighting the diffusion MRI signal is affected by intravoxel incoherent motion (IVIM) caused by dephasing of magnetization due to incoherent blood flow in capillaries or other sources of microcirculation. While IVIM measurements at low diffusion weightings have been frequently used to investigate perfusion in the body as well as in malignant tissue, the effect and origin of IVIM in normal brain tissue is not completely established. We investigated the IVIM effect on the brain diffusion MRI signal in a cohort of 137 radiologically-normal patients (62 male; mean age = 50.2 ± 17.8, range = 18 to 94). We compared the diffusion tensor parameters estimated from a mono-exponential fit at b = 0 and 1000 s/mm² versus at b = 250 and 1000 s/mm². The asymptotic fitting method allowed for quantitative assessment of the IVIM signal fraction f* in specific brain tissue and regions. Our results show a mean (median) percent difference in the mean diffusivity of about 4.5 (4.9)% in white matter (WM), about 7.8 (8.7)% in cortical gray matter (GM), and 4.3 (4.2)% in thalamus. Corresponding perfusion fraction f* was estimated to be 0.033 (0.032) in WM, 0.066 (0.065) in cortical GM, and 0.033 (0.030) in the thalamus. The effect of f* with respect to age was found to be significant in cortical GM (Pearson correlation ρ = 0.35, p = 3*10^-5) and the thalamus (Pearson correlation ρ = 0.20, p = 0.022) with an average increase in f* of 5.17*10^-4/year and 3.61*10^-4/year, respectively. Significant correlations between f* and age were not observed for WM, and corollary analysis revealed no effect of gender on f*. Possible origins of the IVIM effect in normal brain tissue are discussed.

BACKGROUND AND PURPOSE/OBJECTIVE:Diagnostic errors in radiology are classified as perception or interpretation errors. This study determined whether specific conditions differed when perception or interpretation errors occurred during neuroradiology image interpretation. MATERIALS AND METHODS/METHODS:In a sample of 254 clinical error cases in diagnostic neuroradiology, we classified errors as perception or interpretation errors, then characterized imaging technique, interpreting radiologist's experience, anatomic location of the abnormality, disease etiology, time of day, and day of the week. Interpretation and perception errors were compared with hours worked per shift, cases read per shift, average cases read per shift hour, and the order of case during the shift when the error occurred. RESULTS:= .04). CONCLUSIONS:Among diagnostic neuroradiology error cases, interpretation-versus-perception errors are affected by the neuroradiologist's experience, technique, and the volume and rate of cases read. Recognition of these risk factors may help guide programs for error reduction in clinical neuroradiology services.

BACKGROUND AND PURPOSE/OBJECTIVE:The basal forebrain contains multiple structures of great interest to emerging functional neurosurgery applications, yet many neuroradiologists are unfamiliar with this neuroanatomy because it is not resolved with current clinical MR imaging. MATERIALS AND METHODS/METHODS:= 13) to demonstrate and characterize the detailed anatomy of the basal forebrain using a clinical 3T MR imaging scanner. We measured the size of selected internal myelinated pathways and measured subthalamic nucleus size, oblique orientation, and position relative to the intercommissural point. RESULTS:= .084 and .047, respectively). Individual variability for the subthalamic nucleus was greatest for angulation within the sagittal plane (range, 15°-37°), transverse dimension (range, 2-6.7 mm), and most inferior border (range, 4-7 mm below the intercommissural plane). CONCLUSIONS:Direct identification of basal forebrain structures in multiple planes using the TSE T2 sequence makes this challenging neuroanatomy more accessible to practicing neuroradiologists. This protocol can be used to better define individual variations relevant to functional neurosurgical targeting and validate/complement advanced MR imaging methods being developed for direct visualization of these structures in living patients.

Diffusion tractography is routinely used to study white matter architecture and brain connectivity in vivo. A key step for successful tractography of neuronal tracts is the correct identification of tract directions in each voxel. Here we propose a fingerprinting-based methodology to identify these fiber directions in Orientation Distribution Functions, dubbed ODF-Fingerprinting (ODF-FP). In ODF-FP, fiber configurations are selected based on the similarity between measured ODFs and elements in a pre-computed library. In noisy ODFs, the library matching algorithm penalizes the more complex fiber configurations. ODF simulations and analysis of bootstrapped partial and whole-brain in vivo datasets show that the ODF-FP approach improves the detection of fiber pairs with small crossing angles while maintaining fiber direction precision, which leads to better tractography results. Rather than focusing on the ODF maxima, the ODF-FP approach uses the whole ODF shape to infer fiber directions to improve the detection of fiber bundles with small crossing angle. The resulting fiber directions aid tractography algorithms in accurately displaying neuronal tracts and calculating brain connectivity.

Aim: Determine if MR-guided FDG-PET reconstruction improves diagnostic accuracy and epileptogenic lesion localization for patients with focal epilepsy. Introduction: Abnormalities detected on MRI or FDG PET alter clinical management and prognosis in patients with focal epilepsy considering surgery (1). Concordant MRI findings are not always present, whereas -80% of adult patients with chronic seizures have FDG PET abnormalities. State-of-art FDG PET, however, remains limited by partial volume effects (PVEs) that reduce sensitivity particularly for extra-temporal epilepsy (2). MR-guided (MRG) PET reconstruction reduces PVEs (3). We tested the hypothesis that MRG PET reconstruction increases correct localization of epileptogenic lesions across readers with different levels of clinical experience.
Method(s): After IRB approval, a neuroradiologist with 1000+ brain PET interpretations identified 26 epilepsy subjects that underwent simultaneous FDG PET-MRI (Siemens Biograph mMR, Siemens Healthcare, Erlangen, Germany) with final adjudicated diagnosis either as normal (N=10) or cortical dysplasia (N=16). PET emission images were reconstructed using conventional OSEM and MRG PET reconstructions (asymmetric Bowsher prior with 3D MPRAGE as anatomical prior image). Then, 3 blinded readers (with 12, 6 & 18 years of experience; respectively) evaluated cases containing either OSEM or MRG PET in the sagittal, axial and coronal planes for each case (MRI data was not provided). Readers determined if there were focal FDG abnormalities consistent with an epileptogenic zone, then assigned ordinal values to image quality (0-3; where 3 was "excellent") and diagnostic confidence (1-3; where 3 = "definite" abnormality or normal study).
Result(s): The figure below shows coronal OSEM and MRG PET reconstructions (A & B respectively) with co-registered MRI (C) - MRG PET better demonstrated the focal FDG abnormality associated with right frontal cortical dysplasia. All 3 readers rated MRG PET images higher in overall quality (2.6 +/- 0.7 vs 2.0 +/- 0.5, Mann-Whitney test, P<0.00001). Reconstruction method did not affect diagnostic confidence (2.6 +/- 0.7 vs 2.9 +/- 0.4, Mann-Whitney test, P=0.555). Readers 2 & 3 (with less experience reading brain FDG PET), improved their localization of the seizure focus using MRG PET images from 42.9 to 75%, and 50 to 75% correct respectively. Reader 1, with the most experience, demonstrated no change in correct localization (85.7 vs 83.3%), but reported more confidence in the diagnosis (P=0.033). Global percentage correct for all 3 raters increased from 59.5% to 77.8% (chi-squared test, P=0.086). MRG PET images increased interpretation sensitivity from 69% to 75%, specificity from 70% to 83% and accuracy from 70% to 78%, but these changes did not reach statistical significance.
Conclusion(s): These initial results demonstrate that MRG PET reconstruction of FDG data can increase correct seizure localization for PET readers with less experience. Study limitations include that clinical history, anatomical correlation and non-attenuation corrected FDG PET images were not available to blinded readers. Future work will increase the number of subjects evaluated by the 3 readers to increase statistical power

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.