Sleep-Disordered Breathing and Idiopathic Normal-Pressure Hydrocephalus: Recent Pathophysiological Advances.

PURPOSE OF REVIEW: Idiopathic normal-pressure hydrocephalus (iNPH) is characterized clinically by ventriculomegaly, abnormal gait, falls, incontinence, and cognitive decline. This article reviews recent advances in the pathophysiology of iNPH concerning sleep-disordered breathing (SDB) and glymphatic circulation during deep sleep. RECENT FINDINGS: The authors found iNPH frequently associated with obstructive sleep apnea (OSA). A critical factor in iNPH is intracranial venous hypertension delaying drainage of cerebrospinal fluid (CSF) into the cerebral venous sinuses. CSF-venous blood circulates in the jugular veins and finally drains into the heart. During SDB, repeated reflex attempts to breathe induce strong respiratory efforts against a closed glottis thereby increasing the negative intrathoracic pressure. This causes atrial distortion and decreases venous return to the heart resulting in retrograde intracranial venous hypertension. Additionally, repeated awakenings from OSA impede sleep-associated circulation of interstitial CSF into the glymphatic circulation contributing to hydrocephalus. Sleep has become a critical element in the cognitive changes of aging including iNPH.

Recovery of Verbal Working Memory Depends on Left Hemisphere White Matter Tracts.

Researchers propose that the recovery of language function following stroke depends on the recruitment of perilesional regions in the left hemisphere and/or homologous regions in the right hemisphere (Kiran, 2012). Many investigations of recovery focus on changes in gray matter regions (e.g., Turkeltaub et al., 2011), whereas relatively few examine white matter tracts (e.g., Schlaug et al., 2009) and none address the role of these tracts in the recovery of verbal working memory (WM). The present study addressed these gaps, examining the role of left vs. right hemisphere tracts in the longitudinal recovery of phonological and semantic WM. For 24 individuals with left hemisphere stroke, we assessed WM performance within one week of stroke (acute timepoint) and at more than six months after stroke (chronic timepoint). To address whether recovery depends on the recruitment of left or right hemisphere tracts, we assessed whether changes in WM were related to the integrity of five white matter tracts in the left hemisphere which had been implicated previously in verbal WM and their right hemisphere analogues. Behavioral results showed significant improvement in semantic but not phonological WM from the acute to chronic timepoints. Improvements in semantic WM significantly correlated with tract integrity as measured by functional anisotropy in the left direct segment of the arcuate fasciculus, inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. The results confirm the role of white matter tracts in language recovery and support the involvement of the left rather than right hemisphere in the recovery of semantic WM.

Recurrent petit mal seizures in Erdheim-Chester disease mimicking an intra-axial brain tumor: illustrative case.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized histologically by foamy histiocytes and Touton giant cells in a background of fibrosis. Bone pain with long bone osteosclerosis is highly specific for ECD. Central nervous system involvement is rare, although dural, hypothalamic, cerebellar, brainstem, and sellar region involvement has been described. OBSERVATIONS: A 59-year-old man with a history of ureteral obstruction, medically managed petit mal seizures, and a left temporal lesion followed with serial magnetic resonance imaging (MRI) presented with worsening seizure control. Repeat MRI identified bilateral amygdala region lesions. Gradual growth of the left temporal lesion over 1 year with increasing seizure frequency prompted resection. A non-Langerhans cell histiocytosis with a BRAF V600E mutation was identified on pathology. Imaging findings demonstrated retroperitoneal fibrosis and long bone osteosclerosis with increased fluorodeoxyglucose uptake that, together with the neuropathologic findings, were diagnostic of ECD. LESSONS: This case of biopsy-proven ECD is unique in that the singular symptom was seizures well controlled with medical management in the presence of similarly located bilateral anterior mesial temporal lobe lesions. Although ECD is rare intracranially, its variable imaging presentation, including the potential to mimic seizure-associated medial temporal lobe tumors, emphasizes the need for a wide differential diagnosis.

NS-HGlio: A generalizable and repeatable HGG segmentation and volumetric measurement AI algorithm for the longitudinal MRI assessment to inform RANO in trials and clinics.

Background: Accurate and repeatable measurement of high-grade glioma (HGG) enhancing (Enh.) and T2/FLAIR hyperintensity/edema (Ed.) is required for monitoring treatment response. 3D measurements can be used to inform the modified Response Assessment in Neuro-oncology criteria. We aim to develop an HGG volumetric measurement and visualization AI algorithm that is generalizable and repeatable. Methods: A single 3D-Convoluted Neural Network, NS-HGlio, to analyze HGG on MRIs using 5-fold cross validation was developed using retrospective (557 MRIs), multicentre (38 sites) and multivendor (32 scanners) dataset divided into training (70%), validation (20%), and testing (10%). Six neuroradiologists created the ground truth (GT). Additional Internal validation (IV, three institutions) using 70 MRIs, and External validation (EV, single institution) using 40 MRIs through measuring the Dice Similarity Coefficient (DSC) of Enh., Ed. ,and Enh. + Ed. (WholeLesion/WL) tumor tissue and repeatability testing on 14 subjects from the TCIA MGH-QIN-GBM dataset using volume correlations between timepoints were performed. Results: IV Preoperative median DSC Enh. 0.89 (SD 0.11), Ed. 0.88 (0.28), WL 0.88 (0.11). EV Preoperative median DSC Enh. 0.82 (0.09), Ed. 0.83 (0.11), WL 0.86 (0.06). IV Postoperative median DSC Enh. 0.77 (SD 0.20), Ed 0.78. (SD 0.09), WL 0.78 (SD 0.11). EV Postoperative median DSC Enh. 0.75 (0.21), Ed 0.74 (0.12), WL 0.79 (0.07). Repeatability testing; Intraclass Correlation Coefficient of 0.95 Enh. and 0.92 Ed. Conclusion: NS-HGlio is accurate, repeatable, and generalizable. The output can be used for visualization, documentation, treatment response monitoring, radiation planning, intra-operative targeting, and estimation of Residual Tumor Volume among others.

Dual Adversarial Attention Mechanism for Unsupervised Domain Adaptive Medical Image Segmentation.

Domain adaptation techniques have been demonstrated to be effective in addressing label deficiency challenges in medical image segmentation. However, conventional domain adaptation based approaches often concentrate on matching global marginal distributions between different domains in a class-agnostic fashion. In this paper, we present a dual-attention domain-adaptative segmentation network (DADASeg-Net) for cross-modality medical image segmentation. The key contribution of DADASeg-Net is a novel dual adversarial attention mechanism, which regularizes the domain adaptation module with two attention maps respectively from the space and class perspectives. Specifically, the spatial attention map guides the domain adaptation module to focus on regions that are challenging to align in adaptation. The class attention map encourages the domain adaptation module to capture class-specific instead of class-agnostic knowledge for distribution alignment. DADASeg-Net shows superior performance in two challenging medical image segmentation tasks.

Diverse data augmentation for learning image segmentation with cross-modality annotations.

The dearth of annotated data is a major hurdle in building reliable image segmentation models. Manual annotation of medical images is tedious, time-consuming, and significantly variable across imaging modalities. The need for annotation can be ameliorated by leveraging an annotation-rich source modality in learning a segmentation model for an annotation-poor target modality. In this paper, we introduce a diverse data augmentation generative adversarial network (DDA-GAN) to train a segmentation model for an unannotated target image domain by borrowing information from an annotated source image domain. This is achieved by generating diverse augmented data for the target domain by one-to-many source-to-target translation. The DDA-GAN uses unpaired images from the source and target domains and is an end-to-end convolutional neural network that (i) explicitly disentangles domain-invariant structural features related to segmentation from domain-specific appearance features, (ii) combines structural features from the source domain with appearance features randomly sampled from the target domain for data augmentation, and (iii) train the segmentation model with the augmented data in the target domain and the annotations from the source domain. The effectiveness of our method is demonstrated both qualitatively and quantitatively in comparison with the state of the art for segmentation of craniomaxillofacial bony structures via MRI and cardiac substructures via CT.

Obstructive hydrocephalus due to aqueductal stenosis from developmental venous anomaly draining bilateral medial thalami: a case report.

Hydrocephalus is a pathological buildup of cerebrospinal fluid within the ventricles leading to ventricular enlargement out of proportion to sulci and subarachnoid spaces. Developmental venous anomaly is a common benign and usually asymptomatic congenital cerebrovascular malformation. Hydrocephalus caused by aqueductal developmental venous anomaly is extremely rare. We describe a case of a 47-year-old man who presents with short-term memory impairment who was found to have a developmental venous anomaly draining bilateral medial thalami through a common collector vein that causes aqueductal stenosis and obstructive hydrocephalus.

One-Shot Generative Adversarial Learning for MRI Segmentation of Craniomaxillofacial Bony Structures.

Compared to computed tomography (CT), magnetic resonance imaging (MRI) delineation of craniomaxillofacial (CMF) bony structures can avoid harmful radiation exposure. However, bony boundaries are blurry in MRI, and structural information needs to be borrowed from CT during the training. This is challenging since paired MRI-CT data are typically scarce. In this paper, we propose to make full use of unpaired data, which are typically abundant, along with a single paired MRI-CT data to construct a one-shot generative adversarial model for automated MRI segmentation of CMF bony structures. Our model consists of a cross-modality image synthesis sub-network, which learns the mapping between CT and MRI, and an MRI segmentation sub-network. These two sub-networks are trained jointly in an end-to-end manner. Moreover, in the training phase, a neighbor-based anchoring method is proposed to reduce the ambiguity problem inherent in cross-modality synthesis, and a feature-matching-based semantic consistency constraint is proposed to encourage segmentation-oriented MRI synthesis. Experimental results demonstrate the superiority of our method both qualitatively and quantitatively in comparison with the state-of-the-art MRI segmentation methods.

Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life.

BACKGROUND: The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. METHODS: Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA), a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. RESULTS: The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine-lysine-bradykinin and labradimil increased the blood half-life of Gd-DTPA sufficiently enough to increase significantly the tumor tissue Gd-DTPA area under the time-concentration curve. CONCLUSION: Metabolically stable bradykinin B2 receptor agonists, methionine-lysine-bradykinin and labradimil, enhance the transvascular delivery of small chemotherapy drugs across the BBTB of malignant gliomas by increasing the blood half-life of the co-infused drug. The selectivity of the increase in drug delivery into the malignant glioma tissue, but not into normal brain tissue or skeletal muscle tissue, is due to the inherent porous nature of the BBTB of malignant glioma microvasculature.

Combinatorial Anatomic and Functional Neural Tract Mapping for Stereotactic Radiosurgery Planning.

Introduction Stereotactic radiosurgery (SRS) is effective and safe for the treatment of the vast majority of brain metastases (BMs). SRS is increasingly used for the simultaneous treatment of multiple lesions, retreatment of recurrence, or subsequent treatment of new lesions. Although radiation injury is relatively uncommon, with the increased utilization of SRS, it is imperative to develop approaches to assess and mitigate radiation-induced neurologic toxicity. Multiple factors influence the development of radiation injury, including patient age, genomic variations, prior treatment, dose and volume treated, and anatomic location. Functional neural structure proximity to SRS targets is a critical factor in developing a systematic integrated risk assessment for SRS patients. Methods We developed an approach for risk assessment based on the combinatorial application of i) the anatomic localization of target lesions using a reference neuroanatomical/functional imaging atlas merged with patient-specific imaging and ii) validation with functional MRI (fMRI) and diffusion tensor imaging MRI (DTI-MRI) to identify neural tracts. Results In the case of a thalamic/midbrain junction breast carcinoma metastasis, the reference image analysis revealed proximity to the corticospinal tract (CST), which was validated by functional DTI-MRI. Dose-volume exposure of the CST could be estimated and considered in the development of a final treatment plan. Conclusion Merging pretreatment MR imaging with neuroanatomical/functional reference MRIs and subsequent validation with fMRI or DTI-MRI may prove to be a valuable approach to screen for neural risks in individual SRS patients. Incorporating this approach in larger studies could further our understanding of dose tolerances in a broad range of neural structures.

Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells.

BACKGROUND: Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. METHODS: Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. RESULTS: We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. CONCLUSION: The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.

Advanced neuroimaging in Balo's concentric sclerosis: MRI, MRS, DTI, and ASL perfusion imaging over 1 year.

Balo concentric sclerosis (BCS) is a rare, atypical demyelinating disease, which may rapidly progress to become severe and fatal. Advanced neuroimaging has proven helpful for early diagnosis, classification, prognostication, and monitoring of progression in multiple sclerosis, but has not been fully explored in BCS. We present the case of a 27-year-old woman with BCS in whom advanced neuroimaging was used to correlate the evolution of disease with clinical findings over the course of 1 year. Magnetic resonance imaging, magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and arterial spin labeling cerebral perfusion were obtained at presentation (Day 0), and at Day 67 and Day 252. Imaging features include multilayered concentric ring lesion, reduced diffusion along the rim, hypoperfusion with possible mild central hyperperfusion, and MRS findings of increased choline, decreased N-acetylaspartate (NAA), and possible presence of lactate and/or lipid peak. DTI tractography and relative apparent diffusion coefficient analyses correlated with clinical symptoms and may help to determine extent of white matter tract injury and prognosis.

Idiopathic normal-pressure hydrocephalus and obstructive sleep apnea are frequently associated: A prospective cohort study.

BACKGROUND: Idiopathic normal-pressure hydrocephalus (iNPH) is defined by ventriculomegaly, cognitive decline, urinary incontinence and gait problems. Vascular risk factors (VRF) are associated with iNPH but obstructive sleep apnea (OSA) -a well-known independent VRF- is seldom mentioned. METHODS: We investigated the presence of sleep-disordered breathing in a prospective cohort of 31 consecutive unselected patients with iNPH using sleep questionnaires and nocturnal polysomnography (PSG). RESULTS: We found OSA in 90·3% (28/31) patients with iNPH; all had undiagnosed sleep abnormalities (snoring, awakenings, nocturia) and excessive daytime sleepiness (Epworth scale = 11·4 ±â€¯6·4; normal <8). Nocturnal PSG showed moderate-to-severe OSA in 25 patients (80·6%) with mean apnea-hypopnea index (AHI) 31·6 ±â€¯23·6/h; mean respiratory distress index (RDI) 34·5/h; and, mean SaO2 desaturation at nadir, 82·2 ±â€¯7·5%. The observed OSA prevalence is statistically significant: 90·3%, 95%CI 74·3-97·5; p = 0·000007. Other VRF included overweight body-mass index (BMI >25- < 30 kg/m2) in 59%, hyperhomocysteinemia 57%, hypertension 43%, hyperlipidemia 39%, diabetes 32%, smoking 21%, coronary disease 18%, and previous stroke 10%. CONCLUSION: Abnormal sleep breathing is frequently associated with iNPH. Validation in larger series is required but we suggest including sleep evaluation in patients suspected of iNPH.

Craniomaxillofacial Bony Structures Segmentation from MRI with Deep-Supervision Adversarial Learning.

Automatic segmentation of medical images finds abundant applications in clinical studies. Computed Tomography (CT) imaging plays a critical role in diagnostic and surgical planning of craniomaxillofacial (CMF) surgeries as it shows clear bony structures. However, CT imaging poses radiation risks for the subjects being scanned. Alternatively, Magnetic Resonance Imaging (MRI) is considered to be safe and provides good visualization of the soft tissues, but the bony structures appear invisible from MRI. Therefore, the segmentation of bony structures from MRI is quite challenging. In this paper, we propose a cascaded generative adversarial network with deep-supervision discriminator (Deep-supGAN) for automatic bony structures segmentation. The first block in this architecture is used to generate a high-quality CT image from an MRI, and the second block is used to segment bony structures from MRI and the generated CT image. Different from traditional discriminators, the deep-supervision discriminator distinguishes the generated CT from the ground-truth at different levels of feature maps. For segmentation, the loss is not only concentrated on the voxel level but also on the higher abstract perceptual levels. Experimental results show that the proposed method generates CT images with clearer structural details and also segments the bony structures more accurately compared with the state-of-the-art methods.

Transulcal parafascicular minimally invasive approach to deep and subcortical cavernomas: technical note.

Cavernomas comprise 8%-15% of intracranial vascular lesions, usually supratentorial in location and superficial. Cavernomas in the thalamus or subcortical white matter represent a unique challenge for surgeons in trying to identify and then use a safe corridor to access and resect the pathology. Previous authors have described specific open microsurgical corridors based on pathology location, often with technical difficulty and morbidity. This series presents 2 cavernomas that were resected using a minimally invasive approach that is less technically demanding and has a good safety profile. The authors report 2 cases of cavernoma: one in the thalamus and brainstem with multiple hemorrhages and the other in eloquent subcortical white matter. These lesions were resected through a transulcal parafascicular approach with a port-based minimally invasive technique. In this series there was complete resection with no neurological complications. The transulcal parafascicular minimally invasive approach relies on image interpretation and trajectory planning, intraoperative navigation, cortical cannulation and subcortical space access, high-quality optics, and resection as key elements to minimize exposure and retraction and maximize tissue preservation. The authors applied this technique to 2 patients with cavernomas in eloquent locations with excellent outcomes.

Technical Pitfalls of Signal Truncation in Perfusion MRI of Glioblastoma.

Dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) is widely used in clinical settings for the radiological diagnosis of brain tumor. The signal change in brain tissue in gradient echo-based DSC PWI is much higher than in spin echo-based DSC PWI. Due to its exquisite sensitivity, gradient echo-based sequence is the preferred method for imaging of all tumors except those near the base of the skull. However, high sensitivity also comes with a dynamic range problem. It is not unusual for blood volume to increase in gene-mediated cytotoxic immunotherapy-treated glioblastoma patients. The increase of fractional blood volume sometimes saturates the MRI signal during first-pass contrast bolus arrival and presents signal truncation artifacts of various degrees in the tumor when a significant amount of blood exists in the image pixels. It presents a hidden challenge in PWI, as this signal floor can be either close to noise level or just above and can go no lower. This signal truncation in the signal intensity time course is a significant issue that deserves attention in DSC PWI. In this paper, we demonstrate that relative cerebral blood volume and relative cerebral blood flow (rCBF) are underestimated due to signal truncation in DSC perfusion, in glioblastoma patients. We propose the use of second-pass tissue residue function in rCBF calculation using least-absolute-deviation deconvolution to avoid the underestimation problem.

Epithelioid glioblastoma presenting as massive intracerebral hemorrhage: Case report and review of the literature.

BACKGROUND: Glioblastoma multiforme (GBM) is a malignant transformation of glial tissue, which presents as intradural, intraaxial lesions with heterogenous contrast enhancement and mass effect. Intratumoral hemorrhage is a common finding in GBM although it is frequently asymptomatic. Massive, symptomatic, intratumoral hemorrhage is uncommon and poses a diagnostic challenge. CASE DESCRIPTION: Here we discuss a case of GBM, which initially presented as massive, symptomatic intracerebral hemorrhage with underlying mass. Due to size of the hemorrhage and poor neurological status the patient was taken to the operating room for evacuation of this hematoma. On pathology, the mass was found to be epithelioid glioblastoma. CONCLUSION: Identification and diagnosis of GBM is generally straightforward. In certain circumstances, the presentation of GBM can vary from the routine. The above case demonstrates how pitfalls in diagnosis can be avoided in order to initiate appropriate therapy.