David Black, Horst K Hahn, Ron Kikinis, Karin Wårdell, and Neda Haj-Hosseini. 2018. Auditory Display for Fluorescence-guided Open Brain Tumor Surgery. Int J Comput Assist Radiol Surg, 13, 1, Pp. 25-35.
PURPOSE: Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon. METHODS: The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants’ verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training. RESULTS: The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate. CONCLUSION: The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful.
Yukiko Saito, Marek Kubicki, Inga Koerte, Tatsui Otsuka, Yogesh Rathi, Ofer Pasternak, Sylvain Bouix, Ryan Eckbo, Zora Kikinis, Christian Clemm von Hohenberg, Tomohide Roppongi, Elisabetta Del Re, Takeshi Asami, Sang-Hyuk Lee, Sarina Karmacharya, Raquelle I Mesholam-Gately, Larry J Seidman, James Levitt, Robert W McCarley, Martha E Shenton, and Margaret A Niznikiewicz. 2018. Impaired White Matter Connectivity between Regions Containing Mirror Neurons, and Relationship to Negative Symptoms and Social Cognition, in Patients with First-Episode Schizophrenia. Brain Imaging Behav, 12, 1, Pp. 229-37.
In schizophrenia, abnormalities in structural connectivity between brain regions known to contain mirror neurons and their relationship to negative symptoms related to a domain of social cognition are not well understood. Diffusion tensor imaging (DTI) scans were acquired in 16 patients with first episode schizophrenia and 16 matched healthy controls. FA and Trace of the tracts interconnecting regions known to be rich in mirror neurons, i.e., anterior cingulate cortex (ACC), inferior parietal lobe (IPL) and premotor cortex (PMC) were evaluated. A significant group effect for Trace was observed in IPL-PMC white matter fiber tract (F (1, 28) = 7.13, p = .012), as well as in the PMC-ACC white matter fiber tract (F (1, 28) = 4.64, p = .040). There were no group differences in FA. In addition, patients with schizophrenia showed a significant positive correlation between the Trace of the left IPL-PMC white matter fiber tract, and the Ability to Feel Intimacy and Closeness score (rho = .57, p = 0.034), and a negative correlation between the Trace of the left PMC-ACC and the Relationships with Friends and Peers score (rho = remove -.54, p = 0.049). We have demonstrated disrupted white mater microstructure within the white matter tracts subserving brain regions containing mirror neurons. We further showed that such structural disruptions might impact negative symptoms and, more specifically, contribute to the inability to feel intimacy (a measure conceptually related to theory of mind) in first episode schizophrenia. Further studies are needed to understand the potential of our results for diagnosis, prognosis and therapeutic interventions.
T Guttuso, Niels Bergsland, J Hagemeier, D G Lichter, Ofer Pasternak, and R Zivadinov. 2018. Substantia Nigra Free Water Increases Longitudinally in Parkinson Disease. AJNR Am J Neuroradiol, 39, 3, Pp. 479-84.
BACKGROUND AND PURPOSE: Free water in the posterior substantia nigra obtained from a bi-tensor diffusion MR imaging model has been shown to significantly increase over 1- and 4-year periods in patients with early-stage idiopathic Parkinson disease compared with healthy controls, which suggests that posterior substantia nigra free water may be an idiopathic Parkinson disease progression biomarker. Due to the known temporal posterior-to-anterior substantia nigra degeneration in idiopathic Parkinson disease, we assessed longitudinal changes in free water in both the posterior and anterior substantia nigra in patients with later-stage idiopathic Parkinson disease and age-matched healthy controls for comparison. MATERIALS AND METHODS: Nineteen subjects with idiopathic Parkinson disease and 19 age-matched healthy control subjects were assessed on the same 3T MR imaging scanner at baseline and after approximately 3 years. RESULTS: Baseline mean idiopathic Parkinson disease duration was 7.1 years. Both anterior and posterior substantia nigra free water showed significant intergroup differences at baseline (< .001 and= .014, respectively, idiopathic Parkinson disease versus healthy controls); however, only anterior substantia nigra free water showed significant longitudinal group × time interaction increases (= .021, idiopathic Parkinson disease versus healthy controls). There were no significant longitudinal group × time interaction differences found for conventional diffusion tensor imaging or free water-corrected DTI assessments in either the anterior or posterior substantia nigra. CONCLUSIONS: Results from this study provide further evidence supporting substantia nigra free water as a promising disease-progression biomarker in idiopathic Parkinson disease that may help to identify disease-modifying therapies if used in future clinical trials. Our novel finding of longitudinal increases in anterior but not posterior substantia nigra free water is potentially a result of the much longer disease duration of our cohort compared with previously studied cohorts and the known posterior-to-anterior substantia nigra degeneration that occurs over time in idiopathic Parkinson disease.
Marco Duering, Sofia Finsterwalder, Ebru Baykara, Anil Man Tuladhar, Benno Gesierich, Marek J Konieczny, Rainer Malik, Nicolai Franzmeier, Michael Ewers, Eric Jouvent, Geert Jan Biessels, Reinhold Schmidt, Frank-Erik de Leeuw, Ofer Pasternak, and Martin Dichgans. 2018. Free Water Determines Diffusion Alterations and Clinical Status in Cerebral Small Vessel Disease. Alzheimers Dement, 14, Pp. 764-74.
INTRODUCTION: Diffusion tensor imaging detects early tissue alterations in Alzheimer’s disease and cerebral small vessel disease (SVD). However, the origin of diffusion alterations in SVD is largely unknown. METHODS: To gain further insight, we applied free water (FW) imaging to patients with genetically defined SVD (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL], n = 57), sporadic SVD (n = 444), and healthy controls (n = 28). We modeled freely diffusing water in the extracellular space (FW) and measures reflecting fiber structure (tissue compartment). We tested associations between these measures and clinical status (processing speed and disability). RESULTS: Diffusion alterations in SVD were mostly driven by increased FW and less by tissue compartment alterations. Among imaging markers, FW showed the strongest association with clinical status (Rup to 34%, P < .0001). Findings were consistent across patients with CADASIL and sporadic SVD. DISCUSSION: Diffusion alterations and clinical status in SVD are largely determined by extracellular fluid increase rather than alterations of white matter fiber organization.
Walid I Essayed, Prashin Unadkat, Ahmed Hosny, Sarah Frisken, Marcio S Rassi, Srinivasan Mukundan, James C Weaver, Ossama Al-Mefty, Alexandra J Golby, and Ian F Dunn. 2018. 3D Printing and Intraoperative Neuronavigation Tailoring for Skull Base Reconstruction after Extended Endoscopic Endonasal Surgery: Proof of Concept. J Neurosurg, Pp. 1-8.
OBJECTIVE Endoscopic endonasal approaches are increasingly performed for the surgical treatment of multiple skull base pathologies. Preventing postoperative CSF leaks remains a major challenge, particularly in extended approaches. In this study, the authors assessed the potential use of modern multimaterial 3D printing and neuronavigation to help model these extended defects and develop specifically tailored prostheses for reconstructive purposes. METHODS Extended endoscopic endonasal skull base approaches were performed on 3 human cadaveric heads. Preprocedure and intraprocedure CT scans were completed and were used to segment and design extended and tailored skull base models. Multimaterial models with different core/edge interfaces were 3D printed for implantation trials. A novel application of the intraoperative landmark acquisition method was used to transfer the navigation, helping to tailor the extended models. RESULTS Prostheses were created based on preoperative and intraoperative CT scans. The navigation transfer offered sufficiently accurate data to tailor the preprinted extended skull base defect prostheses. Successful implantation of the skull base prostheses was achieved in all specimens. The progressive flexibility gradient of the models’ edges offered the best compromise for easy intranasal maneuverability, anchoring, and structural stability. Prostheses printed based on intraprocedure CT scans were accurate in shape but slightly undersized. CONCLUSIONS Preoperative 3D printing of patient-specific skull base models is achievable for extended endoscopic endonasal surgery. The careful spatial modeling and the use of a flexibility gradient in the design helped achieve the most stable reconstruction. Neuronavigation can help tailor preprinted prostheses.
Simon McCarthy-Jones, Lena K L Oestreich, Amanda E Lyall, Zora Kikinis, Dominick T Newell, Peter Savadjiev, Martha E Shenton, Marek Kubicki, Ofer Pasternak, Thomas J Whitford, and Australian Schizophrenia Research Bank. 2018. Childhood Adversity Associated with White Matter Alteration in the Corpus Callosum, Corona Radiata, and Uncinate Fasciculus of Psychiatrically Healthy Adults. Brain Imaging Behav, 12, 2, Pp. 449-58.
Diffusion tensor imaging studies report childhood adversity (CA) is associated with reduced fractional anisotropy (FA) in multiple white matter tracts in adults. Reduced FA may result from changes in tissue, suggesting myelin/axonal damage, and/or from increased levels of extracellular free-water, suggesting atrophy or neuroinflammation. Free-water imaging can separately identify FA in tissue (FA) and the fractional volume of free-water (FW). We tested whether CA was associated with altered FA, FA, and FW in seven white matter regions of interest (ROI), in which FA changes had been previously linked to CA (corona radiata, corpus callosum, fornix, cingulum bundle: hippocampal projection, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus). Tract-based spatial statistics were performed in 147 psychiatrically healthy adults who had completed a self-report questionnaire on CA primarily stemming from parental maltreatment. ROI were extracted according to the protocol provided by the ENIGMA-DTI working group. Analyses were performed both treating CA as a continuous and a categorical variable. CA was associated with reduced FA in all ROI (although categorical analyses failed to find an association in the fornix). In contrast, CA was only associated with reduced FAin the corona radiata, corpus callosum, and uncinate fasciculus (with the continuous measure of CA finding evidence of a negative relation between CA and FAin the fornix). There was no association between CA on FW in any ROI. These results provide preliminary evidence that childhood adversity is associated with changes to the microstructure of white matter itself in adulthood. However, these results should be treated with caution until they can be replicated by future studies which address the limitations of the present study.
Shujing Yao, Jiashu Zhang, Yining Zhao, Yuanzheng Hou, Xinghua Xu, Zhizhong Zhang, Ron Kikinis, and Xiaolei Chen. 2018. Multimodal Image-Based Virtual Reality Presurgical Simulation and Evaluation for Trigeminal Neuralgia and Hemifacial Spasm. World Neurosurg, 113, Pp. e499-e507.
OBJECTIVE: To address the feasibility and predictive value of multimodal image-based virtual reality in detecting and assessing features of neurovascular confliction (NVC), particularly regarding the detection of offending vessels, degree of compression exerted on the nerve root, in patients who underwent microvascular decompression for nonlesional trigeminal neuralgia and hemifacial spasm (HFS). METHODS: This prospective study includes 42 consecutive patients who underwent microvascular decompression for classic primary trigeminal neuralgia or HFS. All patients underwent preoperative 1.5-T magnetic resonance imaging (MRI) with T2-weighted three-dimensional (3D) sampling perfection with application-optimized contrasts by using different flip angle evolutions, 3D time-of-flight magnetic resonance angiography, and 3D T1-weighted gadolinium-enhanced sequences in combination, whereas 2 patients underwent extra experimental preoperative 7.0-T MRI scans with the same imaging protocol. Multimodal MRIs were then coregistered with open-source software 3D Slicer, followed by 3D image reconstruction to generate virtual reality (VR) images for detection of possible NVC in the cerebellopontine angle. Evaluations were performed by 2 reviewers and compared with the intraoperative findings. RESULTS: For detection of NVC, multimodal image-based VR sensitivity was 97.6% (40/41) and specificity was 100% (1/1). Compared with the intraoperative findings, the κ coefficients for predicting the offending vessel and the degree of compression were >0.75 (P < 0.001). The 7.0-T scans have a clearer view of vessels in the cerebellopontine angle, which may have significant impact on detection of small-caliber offending vessels with relatively slow flow speed in cases of HFS. CONCLUSIONS: Multimodal image-based VR using 3D sampling perfection with application-optimized contrasts by using different flip angle evolutions in combination with 3D time-of-flight magnetic resonance angiography sequences proved to be reliable in detecting NVC and in predicting the degree of root compression. The VR image-based simulation correlated well with the real surgical view.
Jeffrey P Guenette, Robert A Stern, Yorghos Tripodis, Alicia S Chua, Vivian Schultz, Valerie J Sydnor, Nathaniel Somes, Sarina Karmacharya, Christian Lepage, Pawel Wrobel, Michael L Alosco, Brett M Martin, Christine E Chaisson, Michael J Coleman, Alexander P Lin, Ofer Pasternak, Nikos Makris, Martha E Shenton, and Inga K Koerte. 2018. Automated versus Manual Segmentation of Brain Region Volumes in Former Football Players. Neuroimage Clin, 18, Pp. 888-96.
Objectives: To determine whether or not automated FreeSurfer segmentation of brain regions considered important in repetitive head trauma can be analyzed accurately without manual correction. Materials and methods: 3 T MR neuroimaging was performed with automated FreeSurfer segmentation and manual correction of 11 brain regions in former National Football League (NFL) players with neurobehavioral symptoms and in control subjects. Automated segmentation and manually-corrected volumes were compared using an intraclass correlation coefficient (ICC). Linear mixed effects regression models were also used to estimate between-group mean volume comparisons and to correlate former NFL player brain volumes with neurobehavioral factors. Results: Eighty-six former NFL players (55.2 ± 8.0 years) and 22 control subjects (57.0 ± 6.6 years) were evaluated. ICC was highly correlated between automated and manually-corrected corpus callosum volumes (0.911), lateral ventricular volumes (right 0.980, left 0.967), and amygdala-hippocampal complex volumes (right 0.713, left 0.731), but less correlated when amygdalae (right -0.170, left -0.090) and hippocampi (right 0.539, left 0.637) volumes were separately delineated and also less correlated for cingulate gyri volumes (right 0.639, left 0.351). Statistically significant differences between former NFL player and controls were identified in 8 of 11 regions with manual correction but in only 4 of 11 regions without such correction. Within NFL players, manually corrected brain volumes were significantly associated with 3 neurobehavioral factors, but a different set of 3 brain regions and neurobehavioral factor correlations was observed for brain region volumes segmented without manual correction. Conclusions: Automated FreeSurfer segmentation of the corpus callosum, lateral ventricles, and amygdala-hippocampus complex may be appropriate for analysis without manual correction. However, FreeSurfer segmentation of the amygdala, hippocampus, and cingulate gyrus need further manual correction prior to performing group comparisons and correlations with neurobehavioral measures.
Vincent Koppelmans, Jessica M Scott, Meghan E Downs, Kaitlin E Cassady, Peng Yuan, Ofer Pasternak, Scott J Wood, Yiri E De Dios, Nichole E Gadd, Igor Kofman, Roy Riascos, Patricia A Reuter-Lorenz, Jacob J Bloomberg, Ajitkumar P Mulavara, Lori L Ploutz-Snyder, and Rachael D Seidler. 2018. Exercise Effects on Bed Rest-induced Brain Changes. PLoS One, 13, 10, Pp. e0205515.
PURPOSE: Spaceflight negatively affects sensorimotor behavior; exercise mitigates some of these effects. Head down tilt bed rest (HDBR) induces body unloading and fluid shifts, and is often used to investigate spaceflight effects. Here, we examined whether exercise mitigates effects of 70 days HDBR on the brain and if fitness and brain changes with HDBR are related. METHODS: HDBR subjects were randomized to no-exercise (n = 5) or traditional aerobic and resistance exercise (n = 5). Additionally, a flywheel exercise group was included (n = 8). Exercise protocols for exercise groups were similar in intensity, therefore these groups were pooled in statistical analyses. Pre and post-HDBR MRI (structure and structural/functional connectivity) and physical fitness measures (lower body strength, muscle cross sectional area, VO2 max, body composition) were collected. Voxel-wise permutation analyses were used to test group differences in brain changes, and their associations with fitness changes. RESULTS: Comparisons of exercisers to controls revealed that exercise led to smaller fitness deterioration with HDBR but did not affect brain volume or connectivity. Group comparisons showed that exercise modulated post-HDBR recovery of brain connectivity in somatosensory regions. Posthoc analysis showed that this was related to functional connectivity decrease with HDBR in non-exercisers but not in exercisers. Correlational analyses between fitness and brain changes showed that fitness decreases were associated with functional connectivity and volumetric increases (all r >.74), potentially reflecting compensation. Modest brain changes or even decreases in connectivity and volume were observed in subjects who maintained or showed small fitness gains. These results did not survive Bonferroni correction, but can be considered meaningful because of the large effect sizes. CONCLUSION: Exercise performed during HDBR mitigates declines in fitness and strength. Associations between fitness and brain connectivity and volume changes, although unadjusted for multiple comparisons in this small sample, suggest that supine exercise reduces compensatory HDBR-induced brain changes.