Contralateral Region Research Articles

The Insula Modulates the Effects of Aerobic Training on Cardiovascular Function and Ambulation in Multiple Sclerosis (P10-3.010)

<h3>Objective:</h3> To understand the effects of aerobic training (AT), focusing on the role of insula (differentiating in right and left) in establishing cardiovascular fitness (CF) and AT responses in people with multiple sclerosis (pwMS). <h3>Background:</h3> Impairment in the autonomic control of cardiovascular function is very common in pwMS. Insula is a key region related to this function with differences between left and right hemisphere. Insula lesions and atrophy are frequent in pwMS and appear to be related to cardiovascular alterations. AT targets the cardiopulmonary system and is proposed as a neuroprotective strategy in several neurological conditions. <h3>Design/Methods:</h3> Sixty-one pwMS were randomized in two groups (MS-AT and MS-C) to perform 24 training sessions of 30–40 minutes for 2–3 times per week. MS-AT performed moderate AT, while MS-C underwent non-specific motor training. All patients had a baseline and follow-up evaluation after the training period, including assessment of maximal peak of oxygen consumption (VO2max), heart rate reserve (HRR), 6-minute walk test (6MWT) and a MRI scan to quantify lesion volumes (LV), global and regional brain atrophy. Two age- and sex-matched healthy control (HC) groups were enrolled for baseline comparison of CF and brain volumetry data. <h3>Results:</h3> At baseline, MS patients showed impaired values of VO2max, HRR and 6MWT (p&lt;0.001) and a widespread pattern of atrophy compared to HC, including bilateral insula. In MS, higher left insula LV correlated to higher HRR (R=0.27, p&lt;0.05). After training, MS-AT experienced an improvement in 6MWT compared to MS-C and this enhancement was greater in patients without insular lesions. At follow-up, MS-C showed a reduction of left anterior insula volume compared to baseline (p&lt;0.001). <h3>Conclusions:</h3> In pwMS, AT improves CF and walking capacity. It showed a neuroprotective effect, especially for the left insula that has a stronger relationship with CF, compared to the contralateral region. <b>Disclosure:</b> Dr. Albergoni has nothing to disclose. Loredana Storelli has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Imaging biomarkers of cerebral edema automatically extracted from routine CT scans of large vessel occlusion strokes.

Volumetric and densitometric biomarkers have been proposed to better quantify cerebral edema after stroke, but their relative performance has not been rigorously evaluated. Patients with large vessel occlusion stroke from three institutions were analyzed. An automated pipeline extracted brain, cerebrospinal fluid (CSF), and infarct volumes from serial CTs. Several biomarkers were measured: change in global CSF volume from baseline (ΔCSF); ratio of CSF volumes between hemispheres (CSF ratio); and relative density of infarct region compared with mirrored contralateral region (net water uptake [NWU]). These were compared to radiographic standards, midline shift and relative hemispheric volume (RHV) and malignant edema, defined as deterioration resulting in need for osmotic therapy, decompressive surgery, or death. We analyzed 255 patients with 210 baseline CTs, 255 24-hour CTs, and 81 72-hour CTs. Of these, 35 (14%) developed malignant edema and 63 (27%) midline shift. CSF metrics could be calculated for 310 (92%), while NWU could only be obtained from 193 (57%). Peak midline shift was correlated with baseline CSF ratio (ρ=-.22) and with CSF ratio and ΔCSF at 24 hours (ρ=-.55/.63) and 72 hours (ρ=-.66/.69), but not with NWU (ρ=.15/.25). Similarly, CSF ratio was correlated with RHV (ρ=-.69/-.78), while NWU was not. Adjusting for age, National Institutes of Health Stroke Scale, tissue plasminogen activator treatment, and Alberta Stroke Program Early CT Score, CSF ratio (odds ratio [OR]:1.95 per 0.1, 95% confidence interval [CI]: 1.52-2.59) and ΔCSF at 24 hours (OR:1.87 per 10%, 95% CI: 1.47-2.49) were associated with malignant edema. CSF volumetric biomarkers can be automatically measured from almost all routine CTs and correlate better with standard edema endpoints than net water uptake.

Abstract 2882: Characteristic immunomodulatory role of myeloid galectin-9 in the brain tumor microenvironment

Abstract Galectin-9 is a member of galectin family with carbohydrate-recognition domains that specifically bind to β-galactoside. Increasing reports have suggested that galectin-9 can bind and interact with immune-modulatory molecules including TIM-3 in several pathophysiological conditions, especially in T cells. However, to date, little is known about the galectin-9 in myeloid cells under tumor microenvironment. In this study, we explored the expressional characteristics and roles of galectin-9 in the brain tumor microenvironment using an intracranial mouse brain tumor model and in vitro system. We found that expression level of galectin-9 was markedly elevated in ipsilateral hemisphere compared to contralateral hemisphere of intracranial brain tumor model. FACS analyses showed that galectin-9 expression was higher in CD45highCD11bhigh macrophages and CD45midCD11bhigh microglia as well as lymphocytes from ipsilateral region than those from contralateral region. In addition, galectin-9 levels were increased after exposure to GL26 brain tumor cells in in vitro co-culture system using primary microglia. Interestingly, phagocytic activity, a key function of myeloid cells, was significantly reduced in galecin-9+ microglia compared to galecin-9- microglia when co-cultured with GL26-GFP cells. Furthermore, SIRPα levels were higher in galectin-9+ microglia than galecin-9- microglia. Similar results were observed in macrophages. Collectively, these findings suggest that galectin-9 may be an important modulatory molecule in myeloid cells under brain tumor microenvironment. Citation Format: Chanju Lee, Dahee Yu, Eun Jung Park. Characteristic immunomodulatory role of myeloid galectin-9 in the brain tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2882.

Inguinal Hernia; Open Surgery Vs Laparoscopy

The past 50 years, surgeons have wrestled with the question regarding the contralateral inguinal region in an infant or child with a known unilateral in guinalhernia. Repair one side or both. Laparoscopic hernia repair is an effective and increasingly popular alternative to open herniotomy.

Repetitive Negative Thinking–Specific and –Nonspecific White Matter Tracts Engaged by Historical Psychosurgical Targets for Depression

BackgroundRepetitive negative thinking (RNT) is a frequent symptom of major depressive disorder (MDD) that is associated with poor outcomes and treatment resistance. While most studies on RNT have focused on structural and functional characteristics of gray matter, this study aimed to examine the association between white matter (WM) tracts and interindividual variability in RNT. MethodsA probabilistic tractography approach was used to characterize differences in the size and anatomical trajectory of WM fibers traversing psychosurgery targets historically useful in the treatment of MDD (anterior capsulotomy, anterior cingulotomy, and subcaudate tractotomy) in patients with MDD and low (n = 53) or high (n = 52) RNT, and healthy control subjects (n = 54). MDD samples were propensity matched on depression and anxiety severity and demographics. ResultsWM tracts traversing left hemisphere targets and reaching the ventral anterior body of the corpus callosum (thus extending to contralateral regions) were larger in the high-RNT MDD group compared with low-RNT (effect size D = 0.27, p = .042) and healthy control (D = 0.23, p = .02) groups. MDD was associated with greater size of tracts that converge onto the right medial orbitofrontal cortex regardless of RNT intensity. Other RNT-nonspecific findings in MDD involved tracts reaching the left primary motor and right primary somatosensory cortices. ConclusionsThis study provides the first evidence to our knowledge that WM connectivity patterns, which could become targets of intervention, differ between high- and low-RNT participants with MDD. These WM differences extend to circuits that are not specific to RNT, possibly subserving reward mechanisms and psychomotor activity.

Three-Dimensional Composite Heatmaps of Unilateral Lambdoid Synostosis and Deformational Plagiocephaly

Background: The differentiation of unilateral lambdoid synostosis (ULS) and deformational plagiocephaly (DP) is vital to provide appropriate treatment intervention. Three-dimensional (3D) photo grammetry provides rapid, reproducible image capture without radiation exposure. Advanced analytical methods can help identify distinctive features to differentiate the two craniofacial conditions. This study uses 3D photogrammetry of ULS and DP patients to analyze the global cranial morphology for diagnostic differentiation. Methods: A retrospective review of 3D photogrammetry of 19 ULS and 25 DP patients were analyzed. Cranial vault asymmetry index, oblique cranial length ratio, and diagonal difference were measured. 3D photogrammetry-based composites were created and overlaid on age and gender-matched controls to generate heat maps representing morphologic differences in contour. Results: Cranial vault asymmetry index and oblique cranial length ratio were significantly different between ULS and DP (0.019; 0.022). 3D photogrammetry ULS composite showed retrusion in the ipsilateral occipitoparietal area, contralateral posterior parietal projection, contralateral frontal projection, relative ipsilateral mastoid bulge, and facial projection. DP composite showed unilateral occipital projection and contralateral anterior projection. The contralateral occipital regions in the occipital and anterior areas remained equivocal to control patients. Conclusions: Diagnostic differentiation of ULS and DP has previously relied on observation and linear measurements of cranial asymmetry in a single plane. 3D photogrammetry composites provide a global contour evaluation for diagnosis and longitudinal outcome analysis.

Preclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates.

Currently, there are multiple active clinical trials involving poly(ADP-ribose) polymerase (PARP) inhibitors in the treatment of glioblastoma. The noninvasive quantification of baseline PARP expression using positron emission tomography (PET) may provide prognostic information and lead to more precise treatment. Due to the lack of brain-penetrant PARP imaging agents, the reliable and accurate in vivo quantification of PARP in the brain remains elusive. Herein, we report the synthesis of a brain-penetrant PARP PET tracer, (R)-2-(2-methyl-1-(methyl-11C)pyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide ([11C]PyBic), and its preclinical evaluations in a syngeneic RG2 rat glioblastoma model and healthy nonhuman primates. We synthesized [11C]PyBic using veliparib as the labeling precursor, performed dynamic PET scans on RG2 tumor-bearing rats and calculated the distribution volume ratio (DVR) using simplified reference region method 2 (SRTM2) with the contralateral nontumor brain region as the reference region. We performed biodistribution studies, western blot, and immunostaining studies to validate the in vivo PET quantification results. We characterized the brain kinetics and binding specificity of [11C]PyBic in nonhuman primates on FOCUS220 scanner and calculated the volume of distribution (VT), nondisplaceable volume of distribution (VND), and nondisplaceable binding potential (BPND) in selected brain regions. [11C]PyBic was synthesized efficiently in one step, with greater than 97% radiochemical and chemical purity and molar activity of 148 ± 85MBq/nmol (n = 6). [11C]PyBic demonstrated PARP-specific binding in RG2 tumors, with 74% of tracer binding in tumors blocked by preinjected veliparib (i.v., 5mg/kg). The in vivo PET imaging results were corroborated by ex vivo biodistribution, PARP1 immunohistochemistry and immunoblotting data. Furthermore, brain penetration of [11C]PyBic was confirmed by quantitative monkey brain PET, which showed high specific uptake (BPND > 3) and low nonspecific uptake (VND < 3mL/cm3) in the monkey brain. [11C]PyBic is the first brain-penetrant PARP PET tracer validated in a rat glioblastoma model and healthy nonhuman primates. The brain kinetics of [11C]PyBic are suitable for noninvasive quantification of available PARP binding in the brain, which posits [11C]PyBic to have broad applications in oncology and neuroimaging.

Organizational Principles of the Centrifugal Projections to the Olfactory Bulb.

Centrifugal projections in the olfactory system are critical to both olfactory processing and behavior. The olfactory bulb (OB), the first relay station in odor processing, receives a substantial number of centrifugal inputs from the central brain regions. However, the anatomical organization of these centrifugal connections has not been fully elucidated, especially for the excitatory projection neurons of the OB, the mitral/tufted cells (M/TCs). Using rabies virus-mediated retrograde monosynaptic tracing in Thy1-Cre mice, we identified that the three most prominent inputs of the M/TCs came from the anterior olfactory nucleus (AON), the piriform cortex (PC), and the basal forebrain (BF), similar to the granule cells (GCs), the most abundant population of inhibitory interneurons in the OB. However, M/TCs received proportionally less input from the primary olfactory cortical areas, including the AON and PC, but more input from the BF and contralateral brain regions than GCs. Unlike organizationally distinct inputs from the primary olfactory cortical areas to these two types of OB neurons, inputs from the BF were organized similarly. Furthermore, individual BF cholinergic neurons innervated multiple layers of the OB, forming synapses on both M/TCs and GCs. Taken together, our results indicate that the centrifugal projections to different types of OB neurons may provide complementary and coordinated strategies in olfactory processing and behavior.

Discrimination between progressive penumbra and benign oligemia of the diffusion-perfusion mismatch region by amide proton transfer-weighted imaging

PurposeAmide proton transfer-weighted (APTw) imaging was an effective tool to reveal the tissue acidosis of acute ischemic stroke. This study aimed to evaluate the ability of APTw MRI to distinguish progressive penumbra and benign oligemia in the diffusion-perfusion mismatch region. Materials and methods38 acute cerebral infarction patients who underwent a comprehensive MRI examination, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), APT imaging, and a follow-up scan in one week were recruited. There were 12 DWI/PWI match cases. The DWI/PWI mismatch patients were divided into 10 progressive cases and 16 stable cases according to the lesion size on the follow-up DWI image compared to the admission scan. Three ROIs: infarction lesion, peripheral, and contralateral normal regions were measured on each subject's MTRasym map. The Friedman test was used to compare the changes of MTRasym among three different regions within each group. The Kruskal-Wallis ANOVA test was used to compare them among the same region of different groups. The correlation between the MTRasym of the peripheral region and the lesion enlargement was analyzed by the Spearman test. ResultsThe MTRasym at the infarction lesion of all three groups showed significant decrease to the contralateral normal tissue. In the progressive mismatch group, the MTRasym at the peripheral region within the DWI/PWI mismatch showed a significant difference with the contralateral normal region and no difference with the infarct core. Whereas both the MTRasym at the peripheral region of the stable mismatch and match groups had no significant difference with the contralateral side, but the differences were significant from those of the central core. When comparing the peripheral region of three groups, the MTRasym of the progressive mismatch group showed a significant decrease to that of the stable mismatch and match groups. The MTRasym of the peripheral region showed a negative correlation with lesion enlargement. ConclusionAPTw imaging is promising to stratify the heterogeneous PWI/DWI mismatch region and benefit the clinical treatment.

The characteristics of brain structural remodeling in patients with unilateral vestibular schwannoma.

Brain structural remodeling alters related brain function. However, few studies have assessed morphological alterations of unilateral vestibular schwannoma (VS) patients. Therefore, this study examined the characteristics of brain structural remodeling in unilateral VS patients. We recruited 39 patients with unilateral VS (19 left, 20 right) and 24 matched normal controls (NCs). We obtained brain structural imaging data using 3T T1-weighted anatomical and diffusion tensor imaging scans. Then, we evaluated both gray and white matter (WM) changes using FreeSurfer software and tract-based spatial statistics, respectively. Furthermore, we constructed a structural covariance network to assess brain structural network properties and the connectivity strength between brain regions. Compared with NCs, VS patients showed cortical thickening in non-auditory areas (e.g., the left precuneus), especially left VS patients, along with reduced cortical thickness in the right superior temporal gyrus (auditory areas). VS patients also showed increased fractional anisotropy in extensive non-auditory-related WM (e.g., the superior longitudinal fasciculus), especially right VS patients. Both left and right VS patients showed increased small-worldness (more efficient information transfer). Left VS patients had a single reduced-connectivity subnetwork in contralateral temporal regions (right-side auditory areas), but increased connectivity between some non-auditory regions (e.g., left precuneus and left temporal pole). VS patients exhibited greater morphological alterations in non-auditory than auditory areas, with structural reductions seen in related auditory areas and a compensatory increase in non-auditory areas. Left and right VS patients show differential patterns of brain structural remodeling. These findings provide a new perspective on the treatment and postoperative rehabilitation of VS.

Association between the morphological features of the central sulcus and the somatomotory representation: anatomo-functional evaluation of neuroplasticity through nTMS.

In recent years navigated transcranial magnetic stimulation (nTMS) has emerged as a useful tool for the preoperative mapping of brain cortical areas surrounding neoplastic tissues allowing for maximal safe tumor resection and minimizing new postoperative permanent neurological deficits. Three patients presenting with an intrinsic brain tumor (one metastasis from mammary carcinoma, one high-grade glioma, and one low-grade glioma) located within or in close relationship to the central sulcus were enrolled for this study. The MRI-based morphological and nTMS mapping of the central sulcus of the intact hemisphere was complemented by the examination of the contralateral region harboring the lesion. The findings were independently compared, in search of evidence of tumor-induced neuroplasticity and/or signs of parenchymal dislocation/infiltration caused by the tumor. An individual description of each mapping session is provided. Significant discrepancies were observed between morphological MRI and functional nTMS mapping in two patients, demonstrating a tumor-induced shift of distinct cortical areas controlling hand and/or facial movements. In the cases of gliomas, a lower MT was detected in the lesioned hemisphere, possibly due to increased electrical excitability caused by the tumor itself. The integration of MRI-based morphological mapping of the central sulcus with the detection of its somatomotor representations through nTMS can assist neurosurgeons when planning the resection of a motor-eloquent tumor, stratifying the risks of secondary neurological deficits. The combination of the two preoperative techniques is able to disclose tumor-induced neural plasticity subsequently guiding a more precise resection.

Abstract 12: Higher Blood Pressure Trajectories After Endovascular Thrombectomy Are Associated With Cerebral Edema Development

Introduction: High blood pressure after endovascular thrombectomy (EVT) can cause cerebral hyperemia and disrupt the blood-brain barrier. However, its role in cerebral edema development is incompletely understood. In this study, we examined the relationship between post-EVT systolic blood pressure (SBP) trajectories and cerebral edema. Methods: We prospectively enrolled patients with large-vessel occlusion stroke who underwent EVT. Cerebrospinal fluid (CSF) volume was measured using a deep-learning algorithm on CT images at baseline, 24 hours, and 72 hours after stroke. The ratio of CSF volumes between hemispheres was calculated. Automated segmentation of infarct regions on follow-up scans was used to measure net water uptake (NWU), the ratio of density within infarcted tissue relative to the mirrored contralateral region. Latent variable mixture modeling (LVMM) divided patients into SBP trajectory groups during the first 72 hours post-EVT (Fig. 1A). Measures of edema (change in CSF ratio, NWU) were compared between groups. Results: One hundred patients (mean age 70 ± 16, mean NIHSS 15) were analyzed. Edema was assessed by a gradual increase in NWU (20.5, 27.0) at 24 and 72 hours, respectively, and by a reduction in CSF ratio (0.95, 0.78, 0.68) in the affected hemisphere at baseline, 24 hours, and 72 hours, respectively. LVMM identified five SBP trajectories. Higher SBP trajectories were associated with higher NWU (Fig. 1B) but not lower CSF ratio at 24 hours (p&lt;0.001 and p=0.343, respectively). After adjusting for age, admission NIHSS, and TICI score, the moderate-to-high and high-to-moderate trajectory groups were independently associated with higher NWU (aOR 11.40, 95% CI 2.14-20.66) and (aOR 10.97, 95% CI 0.12-21.82), relative to the low and moderate groups. Conclusions: Higher SBP trajectories are associated with an increase in NWU post-EVT. NWU is a promising radiographic biomarker for measuring cerebral edema during the early phase after stroke.

Journey to the other side of the brain: asymmetry in patients with chronic mild or moderate traumatic brain injury.

Patients with chronic mild or moderate traumatic brain injury have some regions of brain atrophy (including cerebral white matter) but even more regions of abnormal brain enlargement (including other cerebral regions). Ipsilateral injury and atrophy cause the eventual development of contralateral compensatory hypertrophy. 50 patients with mild or moderate traumatic brain injury were compared to 80 normal controls (n=80) with respect to MRI brain volume asymmetry. Asymmetry-based correlations were used to test the primary hypothesis. The group of patients had multiple regions of abnormal asymmetry. The correlational analyses supported the conclusion that acute injury to ipsilateral cerebral white matter regions caused atrophy, leading eventually to abnormal enlargement of contralateral regions due to compensatory hypertrophy.

Enhancement of motor imagery training efficiency by an online adaptive training paradigm integrated with error related potential

Objective. Motor imagery (MI) is a process of autonomously modulating the motor area to rehearse action mentally without actual execution. Based on the neuroplasticity of the cerebral cortex, MI can promote the functional rehabilitation of the injured cerebral cortex motor area. However, it usually takes several days to a few months to train individuals to acquire the necessary MI ability to control rehabilitation equipment in current studies, which greatly limits the clinical application of rehabilitation training systems based on the MI brain–computer interface (BCI). Approach. A novel MI training paradigm combined with the error related potential (ErrP) is proposed, and online adaptive training of the MI classifier was performed using ErrP. ErrP is used to correct the output of the MI classification to obtain a higher accuracy of kinesthetic feedback based on the imagination intention of subjects while generating simulated labels for MI online adaptive training. In this way, we improved the MI training efficiency. Thirteen subjects were randomly divided into an experimental group using the proposed paradigm and a control group using the traditional MI training paradigm to participate in six MI training experiments. Main results. The proposed paradigm enabled the experimental group to obtain a higher event-related desynchronization modulation level in the contralateral brain region compared with the control group and 69.76% online classification accuracy of MI after three MI training experiments. The online classification accuracy reached 72.76% and the whole system recognized the MI intention of the subjects with an online accuracy of 82.61% after six experiments. Significance. Compared with the conventional unimodal MI training strategy, the proposed approach enables subjects to use the MI-BCI based system directly and achieve a better performance after only three training experiments with training left and right hands simultaneously. This greatly improves the usability of the MI-BCI-based rehabilitation system and makes it more convenient for clinical use.

Fractal analysis of healthy and diseased vasculature in pediatric Moyamoya disease.

Fractal dimension is an objective metric for the notion of structural complexity. We sought to investigate differences in structural complexity between healthy and affected territories of cerebral vasculature in moyamoya, as well as associated scalp vasculature and native transdural collaterals in patients with moyamoya by comparing their respective fractal dimensions. Our cohort consisted of 15 transdural collaterals from 12 patients with unilateral anterior circulation moyamoya. Frames of distal arterial vasculature from internal and external carotid angiograms were selected then automatically segmented and also manually annotated by a cerebrovascular surgeon. In the affected hemisphere, the region with transdural collateral supply was compared to the contralateral region. The resulting skeletonized angiograms were analyzed for their fractal dimensions. We found the average fractal dimension (Df) of the moyamoya-side ICA was 1.82 with slightly different means for the anteroposterial (AP) and lateral views (mean = 1.82; mean = 1.81). The overall mean for healthy cerebral vasculature was also found to be 1.82 (AP: mean = 1.83; lateral: mean = 1.81). Mean Df of native transdural collaterals was found to be 1.82 (AP: mean = 1.83; lateral: mean = 1.81). The mean Df difference between autosegmented and manually segmented images was 0.013. In accordance with the clinical understanding of moyamoya disease, the distal arterial structural complexity is not affected in moyamoya, and is maintained by transdural collaterals formed by vasculogenesis. Autosegmentation of cerebral vasculature is also shown to be accurate when compared to manual segmentation.

Radiomic features of contralateral and ipsilateral hemispheres for prediction of glioma genetic markers

Purpose: Radiomic features of gliomas are often used to predict genetic markers from radiological studies. Radiomic features were extracted from the contralateral brain to test if tumor texture is driving the predictive power of machine learning models. Ideally, these contralateral models would be a negative control for tumor radiomics models, since many studies use contralateral normal appearing white matter for normalization. This study used those features to attempt to predict IDH mutation status, MGMT promoter methylation, TERT promoter mutation, and ATRX mutation status with random forests.Methods: Radiomic features were extracted from the tumor region, a mirrored contralateral region, a spherical region within the tumor, a spherical region on the contralateral, and a spherical sample of the ipsilateral side. These features were used independently to predict IDH, MGMT, TERT, and ATRX using random forests.Main Findings: Contralateral features alone were as predictive of IDH mutation status as tumor features and had predictive power for several genetic markers.Conclusion: Normalization with contralateral brain should be done carefully, and further investigation of potential radiological changes to the contralateral is warranted.

Distribution of intraperitoneally administered deuterium-labeled water in aquaporin-4-knockout mouse brain after middle cerebral artery occlusion.

As the movement of water in the brain is known to be involved in neural activity and various brain pathologies, the ability to assess water dynamics in the brain will be important for the understanding of brain function and the diagnosis and treatment of brain diseases. Aquaporin-4 (AQP4) is a membrane channel protein that is highly expressed in brain astrocytes and is important for the movement of water molecules in the brain. In this study, we investigated the contribution of AQP4 to brain water dynamics by administering deuterium-labeled water (D2O) intraperitoneally to wild-type and AQP4 knockout (AQP4-ko) mice that had undergone surgical occlusion of the middle cerebral artery (MCA). Water dynamics in the infarct region and on either side of the anterior cerebral artery (ACA) was monitored with proton-density-weighted imaging (PDWI) performed on a 7T animal MRI. D2O caused a negative signal change quickly after administration. The AQP4-ko mice showed a delay of the time-to-minimum in both the contralateral and ipsilateral ACA regions compared to wild-type mice. Also, only the AQP4- ko mice showed a delay of the time-to-minimum in the ipsilateral ACA region compared to the contralateral side. In only the wild-type mice, the signal minimum in the ipsilateral ACA region was higher than that in the contralateral ACA region. In the infarct region, the signal attenuation was slower for the AQP4-ko mice in comparison to the wild-type mice. These results suggest that AQP4 loss affects water dynamics in the ACA region not only in the infarct region. Dynamic PDWI after D2O administration may be a useful tool for showing the effects of AQP4 in vivo.

EVALUATION OF METABOLIC RESPONSE IN BONE MARROW LESIONS AFTER EXERCISE IN RELATION TO CHANGES IN ADJACENT CARTILAGE T2 VALUES

Patellofemoral pain syndrome (PFPS) is one of the most common causes of anterior knee pain in active populations. Due to its multifactorial nature, patellofemoral pain is hard to diagnose and treat. Increased stress in the subchondral bone is associated with PFPS and is correlated to elevated bone remodelling. [18F]NaF PET-MR imaging can localize regions of elevated bone remodelling and provide information about the metabolic processes involved (1, 2). Further, [18F]NaF uptake changes after exercise, thus showing that it is sensitive to changes in bone physiology resulting from acute bone loading (3, 4). For cartilage, T2 relaxation times have been used to study cartilage hydration and microstructure changes after exercise. While some studies have observed a decrease in T2 times after exercise, changes are usually transient and have largely been evaluated in the context of healthy subjects (5). An early sign of persistent abnormal mechanical stress is Bone Marrow Lesions (BMLs), which are strongly associated with pain and structural disease progression. We aimed to reproduce prior work which has shown that acute loading results in a large physiological response in bone regions with BMLs. Further, we wanted to explore if there is breakdown of the cartilage microstructure, either at baseline or in response to loading in cartilage regions adjacent to BMLs. The purpose of this study is to detect changes in the functional response of the knee joint to loading using [18F]NaF PET-MR imaging after a stair-climbing exercise in subjects with unilateral patellofemoral pain. The aims of this feasibility study are 1) to detect acute loading-induced changes in [18F]NaF uptake in bone regions with BMLs and 2) compare consequent T2 values in the cartilage adjacent to BMLs at baseline and in response to loading. 4 subjects (3 F, aged 39.5±15.0 years, BMI 26.1±5.9 kg/m2) with unilateral knee pain and BMLs (3 in patella, 1 in femur) underwent two consecutive 30-min [18F]NaF PET/MRI scans of both knees, at baseline and then repeated after a stair-climbing exercise [112 stairs, up and down]. Bone metabolic activity was quantified by calculating maximum standardized uptake values (SUVmax) in areas of BMLs in the painful leg and the corresponding region in the contralateral leg. T2 maps were calculated from quantitative DESS images [TE(1,2)=6.04, 30.44 ms] in the cartilage regions adjacent to the BMLs and in the same regions in the contralateral leg. Segmentations of cartilage were done manually in MATLAB, while SUVmax in BMLs was calculated using ROIs drawn in Horos. Pre- and post-exercise changes in SUVmax and T2 values were compared to account for loading-induced response in both metabolic and structural parameters in painful vs healthy knees. Increased [18F]NaF uptake was observed post-exercise in areas with BMLs (as compared to contralateral leg regions), confirming that PET findings correspond to structural changes observed in MRI (Fig-1). The average SUVmax values increased from 6.35±3.98 to 10.49±5.42 in the painful leg and from 1.71±1.96 to 4.04±3.21 in the contralateral leg after exercise. The average T2 relaxation times increased from 30.61±1.87 ms to 31.61±1.55 ms in the painful leg and from 27.17±2.73 ms to 27.65±2.29 ms in the contralateral leg (Fig-2). The mean change in SUVmax due to exercise was 4.15±2.42 in the BML vs 2.34±2.06 in the contralateral leg. In adjacent cartilage, a mean change in T2 values of 1.01±1.45 ms in the BML region of the painful leg and 0.47±0.48 ms in the contralateral leg was observed. In this feasibility study, [18F]NaF PET-MR showed acute loading-induced changes in BMLs, with a 2-fold increase in SUVmax in the painful leg vs the contralateral leg. While there seemed to be a higher cartilage T2 in regions adjacent to BMLs compared to the contralateral leg, the change induced by exercise was small.

An MRI Study Combining Virtual Brain Grafting and Surface-Based Morphometry Analysis to Investigate Contralateral Alterations in Cortical Morphology in Patients With Diffuse Low-Grade Glioma.

The human brain has ability to reorganize itself in response to glioma. However, the mechanism of cortical reorganization remains unclear. To investigate alterations in cortical thickness and local gyration index (LGI) in patients with unilateral frontal lobe diffuse low-grade glioma (DLGG). Retrospective. Ninety-nine patients with histopathologically proven DLGG invading the left frontal lobe (LF; N=56) or the right frontal lobe (RF; N=43), and healthy controls (HC; N=53). 3.0 T, 3D T1-weighted images and gadolinium enhanced T1-weighted images using magnetization-prepared rapid gradient echo sequence, T2-weighted images, and fluid-attenuated inversion recovery using turbo spin echo sequence. In patients with DLGG, virtual brain grafting combined with Freesurfer was utilized to enable automated cortical thickness and LGI calculation. In HC, standard FreeSurfer pipeline was applied to calculate these measures. Radiomic features were extracted from glioma using Pyradiomic software. General linear model and Pearson's correlation analysis. A P value <0.05 was considered statistically significant. For LF patients, there was significantly increased cortical thickness in the rostral middle frontal gyrus, significantly reduced cortical thickness in the precentral gyrus and hypogyrification in the lingual and medial orbitofrontal (MOF) gyrus in contralateral hemisphere. For RF patients, there was significantly increased cortical thickness in the middle temporal, lateral occipital extending to isthmus cingulate gyrus, significantly reduced cortical thickness in the precentral gyrus and hypogyrification in the lingual gyrus in the contralateral hemisphere. A negative association between four textural features of DLGG and LGI in the right MOF gyrus of LF group was found (r=-0.609, -0.442, -0.545, and -0.417, respectively). Cortical thickness compensation was shown in contralateral homotopic location and some distant contralateral regions. Additionally, there was decreased cortical thickness in the contralateral precentral gyrus and hypogyrification in contralateral lingual gyrus. 4 TECHNICAL EFFICACY: Stage 2.

Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study.

The blood-brain barrier (BBB) controls brain homeostasis; it is formed by vascular endothelial cells that are physically connected by tight junctions (TJs). The BBB expresses efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which limit the passage of substrate molecules from blood circulation to the brain. Focused ultrasound (FUS) with microbubbles can create a local and reversible detachment of the TJs. However, very little is known about the effect of FUS on the expression of efflux transporters. We investigated the in vivo effects of moderate acoustic pressures on both P-gp and BCRP expression for up to two weeks after sonication. Magnetic resonance-guided FUS was applied in the striatum of 12 rats. P-gp and BCRP expression were determined by immunohistochemistry at 1, 3, 7, and 14 days postFUS. Our results indicate that FUS-induced BBB opening is capable of (i) decreasing P-gp expression up to 3 days after sonication in both the treated and in the contralateral brain regions and is capable of (ii) overexpressing BCRP up to 7 days after FUS in the sonicated regions only. Our findings may help improve FUS-aided drug delivery strategies by considering both the mechanical effect on the TJs and the regulation of P-gp and BCRP.