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Purpose: Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a new cancer treatment modality that employs radium-224-loaded metal sources implanted in solid tumors to disperse alpha-emitting atoms within a therapeutic "kill-zone" of a few millimeters around each source. Preclinical studies have demonstrated tumor growth delay in various cancer types, including glioblastoma multiforme, and the method is used in clinical trials for patients with skin and head and neck cancer. This study aims to assess the safety and feasibility of implementing Alpha DaRT for brain tumor treatment in a large animal model., Methods: Alpha-DaRT sources were delivered via image-guided stereotactic implantation into both hemispheres of eight swine. 1-3 layers of radial deployment of 7 sources were delivered through a single penetration point into each hemisphere. A 90-day follow-up period included clinical evaluation, brain MRI, head CT, blood, CSF, urine, and feces sampling, and an analysis of source location over time. Brain tissue pathology was performed on termination., Results: Alpha-DaRT sources were reproducibly and efficiently delivered to the brain cortex and subcortex. No unexpected abnormalities were detected in blood or CSF samples. MRI and CT scans revealed no evidence of major bleeding or infection. Measurements of 212 Pb in blood and CSF exhibited the expected exponential decay from day 7 to day 14 post-source implantation. Minimal spatial and temporal movements of the sources were noted. Histopathological analysis demonstrated locally confined findings in brain parenchyma in a very close proximity to the sources., Conclusion: Alpha-DaRT sources can be safely delivered into a large animal brain using image-guided stereotactic implantation. These findings support further exploration of Alpha DaRT as a potential treatment modality for brain tumors., Competing Interests: Declarations. Competing interests: YS serves as a paid medical advisor for Alpha Tau Medical Ltd. and receives equity. AP serves as a medical advisor for Alpha Tau Medical Ltd. and receives equity. RBD serves as CMO of Alpha Tau Medical Ltd. and receives compensation and equity. LA receives equity and has a research budget funded by the company. All other authors declare no conflict of interest., (© 2024. The Author(s).)

Current guidelines advocate intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) for all patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). We evaluated outcomes with and without IVT pretreatment. Our institutional protocols allow AIS patients presenting early (<4 h from onset or last seen normal) who have an Alberta Stroke Program Early CT Score (ASPECTS) ≥6 to undergo EVT without IVT pretreatment if the endovascular team is in the hospital (direct EVT). Rates of recanalization and hemorrhagic transformation (HT) and neurological outcomes were retrospectively compared in consecutive patients undergoing IVT+EVT vs. direct EVT with subanalyses in those ≥80 years and ≥85 years. In the overall cohort (IVT+EVT = 147, direct EVT = 162), and in subsets of patients ≥80 years (IVT+EVT = 51, direct EVT = 50) and ≥85 years (IVT+EVT = 19, direct EVT = 32), the IVT+EVT cohort and the direct EVT group had similar baseline characteristics, underwent EVT after a comparable interval from symptom onset, and reached similar rates of target vessel recanalization. No differences were observed in the HT frequency, or in disability at discharge or after 90 days. Patients receiving direct EVT underwent more stenting of the carotid artery due to stenosis during the EVT procedure (22% vs. 6%, p = 0.001). Direct EVT and IVT+EVT had comparable neurological outcomes in the overall cohort and in the subgroups of patients ≥80 and ≥85 years, suggesting that direct EVT should be considered in patients with an elevated risk for HT.

Ischemic stroke is a leading cause for neurologic disability worldwide, for which reperfusion is the only available treatment. Neuroimaging in stroke guides treatment, and therefore determines the clinical outcome. However, there are currently no imaging biomarkers for the status of the ischemic brain tissue. Such biomarkers could potentially be useful for guiding treatment in patients presenting with ischemic stroke. Hyperpolarized 13 C MR of [1- 13 C]pyruvate is a clinically translatable method used to characterize tissue metabolism non-invasively in a relevant timescale. The aim of this study was to utilize hyperpolarized [1- 13 C]pyruvate to investigate the metabolic consequences of an ischemic insult immediately during reperfusion and upon recovery of the brain tissue. The rates of lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) were quantified by monitoring the rates of [1- 13 C]lactate and [ 13 C]bicarbonate production from hyperpolarized [1- 13 C]pyruvate. 31 P NMR of the perfused brain slices showed that this system is suitable for studying ischemia and recovery following reperfusion. This was indicated by the levels of the high-energy phosphates (tissue viability) and the chemical shift of the inorganic phosphate signal (tissue pH). Acidification, which was observed during the ischemic insult, has returned to baseline level following reperfusion. The LDH/PDH activity ratio increased following ischemia, from 47.0 ± 12.7 in the control group ( n = 6) to 217.4 ± 121.3 in the ischemia-reperfusion group ( n = 6). Following the recovery period ( ca. 1.5 h), this value had returned to its pre-ischemia (baseline) level, suggesting the LDH/PDH enzyme activity ratio may be used as a potential indicator for the status of the ischemic and recovering brain.

During the 20th century, the average lifespan in the industrialized societies has enormously increased and it is still rising. With the increase in the number of old people, a parallel increase in the number of the disabled elderly is postulated. Thus, the whole society might suffer from an imbalance between the productive segment of the society and a huge segment of helpless people. Moderation of the physiological processes, which enhance disability in aging, turns out to be a major concern in health research and clinical practice. Preservation of brain integrity, which is partly influenced by nutrition, presumably is the main target in the attempt to delay the development of disability of aging. Optimal micronutrient status would moderate the deterioration in brain integrity. The human brain is probably the most vulnerable tissue affected by a long-term unbalanced nutrition and is particularly vulnerable to reactive oxygen species and to oxidative stress, because of its high oxygen requirement, its iron storage capacity and its elevated polyunsaturated fatty acid content, and because of its low synthesis capacity of endogenous antioxidants. The capability of central nervous system (CNS) cells to regenerate is most limited, because their repair is inhibited by anti-apoptotic molecules. Efficient autophagy is the major mechanism that moderates accumulation of aggregating compounds. Autophagy is probably a crucial and a major process in the preservation of brain integrity. Micronutrients (vitamins, trace-elements and also antioxidants) most likely affect brain integrity by normalizing efficient autophagy. Brain sensitivity to metabolic disorders is demonstrated by the effect of homocysteine on metabolic pathways, on brain integrity and on the cognitive capacity. Brain imaging might be used as a surrogate for detecting long-lasting low status of micronutrients. Comprehensive evaluation of brain scans concomitantly with blood micronutrient examinations may provide reliable criteria for the estimation of the optimal micronutrient intakes or blood concentrations. Recommended dietary intakes for micronutrients are based on a list of biomarkers, but have not been suggested a safe range for their intake or blood concentration. According to many studies, a U-shaped curve prevails for the effect of serum calcidiol concentration on the relative risk of morbidity and mortality. An increased relative risk of morbidity and mortality with lower serum calcidiol has been shown in almost all the studies. A safe range of 20-40 ng/mL was identified for serum calcidiol. A significant detrimental effect of serum calcidiol on the hazard ratio for the combined data of all-cause mortality and acute coronary syndrome morbidity was shown at a concentration higher than 36 ng/ml. Most of the tolerable upper intake levels for the micronutrients, published by authorized institutions, were set without considering the long-term effects of overdosing. Excessive intake of almost all the micromutrients, particularly for a long period of time, produces adverse effects. In most of the elderly people prevail an insufficient intake of one or more micronutruients. Therefore, until an efficient laboratory system for evaluating blood levels is established, a moderate 'multivitamin' supplementation at an amount of about half the American RDA for most of the micronutrients is suggested.

Thrombosis via Hunterian ligation, with or without high-flow bypass, is the definitive treatment for unclippable giant aneurysms; however, secondary deterioration may occur. We present a 67-year-old woman with an unclippable giant (33mm) carotid ophthalmic aneurysm. High-flow external carotid artery to middle cerebral artery bypass and proximal cervical internal carotid artery Hunterian ligation achieved complete thrombosis. Subsequent expansion of the thrombosed aneurysm created mass effect with hydrocephalus, leading to marked cognitive and visual decline. Aneurysmal decompression led to improved vision and near-normal neurological function., (2010 Elsevier Ltd. All rights reserved.)

The aim of this study was to correlate clinical and computerized tomography (CT) features of bisphosphonate-related osteonecrosis of the jaws (BRONJ). All ONJ patients for whom there was complete CT scan imaging were eligible. Selected clinical parameters retrieved from their medical records were analyzed for correlation with CT parameters. The clinical presentation of BRONJ was supported by findings in CT imaging in 78.3%. The lesion's size on CT correlated with the presence of purulent secretion (p = 0.03). When sequestrum was present, the median lesion's size on CT was relatively big (28 mm, range 21-43 mm). The mandibular canal cortex was never breached. CT has reasonable detection competence for diagnosing BRONJ. Purulent secretion indicates the likelihood that a more extensive involvement will be displayed on CT. A large lesion on CT should raise the index of suspicion for sequestrum. The CT appearance of a continuous cortex of the mandibular canal may serve as a differential parameter between BRONJ and metastasis to the jaw.

This study presents a novel automatic approach for the identification of anatomical brain structures in magnetic resonance images (MRI). The method combines a fast multiscale multi-channel three dimensional (3D) segmentation algorithm providing a rich feature vocabulary together with a support vector machine (SVM) based classifier. The segmentation produces a full hierarchy of segments, expressed by an irregular pyramid with only linear time complexity. The pyramid provides a rich, adaptive representation of the image, enabling detection of various anatomical structures at different scales. A key aspect of the approach is the thorough set of multiscale measures employed throughout the segmentation process which are also provided at its end for clinical analysis. These features include in particular the prior probability knowledge of anatomic structures due to the use of an MRI probabilistic atlas. An SVM classifier is trained based on this set of features to identify the brain structures. We validated the approach using a gold standard real brain MRI data set. Comparison of the results with existing algorithms displays the promise of our approach.

Objects: The relationship between increased central venous pressure (CVP) and development of hydrocephalus has been extensively discussed in the neuropediatric literature. However, the possibility of a direct connection has not been systematically examined. The purpose of this prospective study was to examine whether there was a correlation between elevated CVP and hydrocephalus in children undergoing cardiac catheterization., Methods: We used cardiac catheterization to measure the right atrial and superior vena caval pressure in 37 children (mean age 30 months) with congenital heart malformations. The children had CVP higher than normal (mean 10.2+/-3.1 mmHg, range 4-18). To evaluate the size of the lateral and fourth ventricles, we performed CT scans of the brain on each child. Abnormal scans were found in 15/37 children, showing brain atrophy (12/37), ventriculomegaly (3/37), and focal infarction (1/37). Cerebral atrophy was more likely to occur in young children (P<0.001). The average head circumference among these children was less than 2SD below the mean for healthy children of comparable ages. Using a correlation coefficient regression model, no relationship was found between CVP and ventricular diameters or head circumference., Conclusions: These results argue against the hypothesis that mild to moderately elevated venous pressure is involved in the mechanism and development of pediatric hydrocephalus.

The pathophysiological mechanisms to explain peritumoral edema have not been clarified. Multiple aspects of brain edema secondary to supratentorial meningiomas were prospectively investigated in a group of 29 patients who underwent surgery consecutively. Sixty-nine tumor samples were analyzed for prostanoid levels. Levels of 6-keto-PGF1 alpha, the stable metabolite of prostacycline, were found to correlate well with the extent of edema (r = 0.51, P < 0.01). The ratio, 6-keto-PGF1 alpha x PGE2/TXB2, was found to have the best correlation with edema index (extension/tumor volume) (r = 0.69, P < 0.005). A case of a hemangiopericytic meningioma with the largest edema extent within the study group also exhibited the highest level of 6-keto-PGF1 alpha (2420 pg/mg protein). Steroid treatment (dosage, duration of therapy, and their product) did not correlate with prostaglandin levels. These findings may explain the inconsistent clinical effects of steroids on meningioma-induced edema. Possible explanations for this phenomenon are discussed. Otherwise, histology, pathological features of tumor aggressiveness, or mechanical parameters, such as its volume, location, and insertion site, did not correlate well with edema parameters or with prostaglandin levels. Similarly, tumor water content, imaging parameters in computed tomography and magnetic resonance, and operative findings (including dissection plane, vascularity, and tumor firmness) did not correlate well with edema parameters. Although a direct cause-effect relationship between prostaglandins and peritumoral edema is not conclusively established, the circumstantial evidence of the ability of prostaglandins to induce vasogenic brain edema and the robust association with peritumoral edema is persuasive.(ABSTRACT TRUNCATED AT 250 WORDS)

A recurrent CNS germinoma with subependymal and spinal metastases was treated by combination of cis-platinum, bleomycin, and vinblastine, resulting in disappearance of intracranial and spinal tumor. Second intracranial relapse responded again to the same combination chemotherapy. Response of spinal metastases to this combination chemotherapy has not been reported previously.