3D surface analysis of hippocampal microvasculature in the irradiated brain

Abstract

Cranial irradiation used to control CNS malignancies can also disrupt the vasculature and impair neurotransmission and cognition. Here we describe two distinct methodologies for quantifying early and late radiation injury in CNS microvasculature. Intravascular fluorescently labeled lectin was used to visualize microvessels in the brain of the irradiated mouse two days post exposure and RECA-1 immunostaining was similarly used to visualize microvessels in the brain of the irradiated rat one month post exposure. Confocal microscopy, image deconvolution and 3-dimensional rendering methods were used to define vascular structure in a ~4×107 µm3 defined region of the brain. Quantitative analysis of these 3D images revealed that irradiation caused significant short- and long-term reductions in capillary density, diameter and volume. In mice, irradiation reduced mean vessel volume from 2,250 to 1,470 µm3 and mean vessel diameter from 5.0 to 4.5 µm, resulting in significant reductions of 34% and 10% respectively. The number of vessel branch points and area was also found to also drop significantly in mice 2 days after irradiation. For rats, immunostaining revealed a significant, 3-fold drop in capillary density 1 month after exposure compared to controls. Such radiation-induced disruption of the CNS microvasculature may be contributory if not causal to any number of neurocognitive side effects that manifest in cancer patients following cranial radiotherapy. This study demonstrates the utility of two distinct methodologies for quantifying these important adverse effects of radiotherapy.

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

“…Typical radiotherapeutic protocols for GBM induce neurocognitive complications, including impairments in learning and memory, attention, and executive function and a variety of mood disorders (5)(6)(7)(8). A breadth of past work from our laboratories has linked adverse neurocognitive outcomes following cranial irradiation to a range of neuropathologies, including reductions in dendritic complexity and spine density (9)(10)(11)(12), reductions in microvascular density (13)(14)(15), reduced myelination and synapse density, and increased neuroinflammation (16,17). These changes are persistent and problematic in the conventionally irradiated brain and have prompted efforts to more fully develop a truly innovative approach to RT, where we have conceptualized and implemented a modality of irradiation named FLASH radiotherapy (FLASH-RT) (18,19).…”

Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation

“…As alluded to above, the typical RT protocols lead to deficits in learning and memory, attention, executive function, and a multitude of mood disorders that can be linked to hippocampal and cortical based alterations [20][21][22]. Many of these detrimental functional outcomes can be tied to a range of associated pathologies that are temporally coincident with reductions in dendritic arborization and spine density, vascular abnormalities, decreases in microvascular density, myelination, and significant increases in neuroinflammation [15,[23][24][25][26]. It is our contention that some (if not all) of these radiation-induced injury signatures are contributory (if not causal) to the long-term manifestation of cognitive impairments.…”

Identification of Alcoholism Based on Wavelet Renyi Entropy and Three‐Segment Encoded Jaya Algorithm

“…Here, we choose a slice vertical to -axis, which is for the convenience of radiologists, since they usually read the axial slices. In the future, we shall develop techniques to handle multislices, and we may develop surface analysis techniques [38].…”