Experiences with computer-assisted detection of cerebral aneurysms in diagnosis by radiologists in real-life clinical environments have not been reported. The purpose of this study was to evaluate ...the usefulness of computer-assisted detection in a routine reading environment.
During 39 months in a routine clinical practice environment, 2701 MR angiograms were each read by 2 radiologists by using a computer-assisted detection system. Initial interpretation was independently made without using the detection system, followed by a possible alteration of diagnosis after referring to the lesion candidate output from the system. We used the final consensus of the 2 radiologists as the reference standard. The sensitivity and specificity of radiologists before and after seeing the lesion candidates were evaluated by aneurysm- and patient-based analyses.
The use of the computer-assisted detection system increased the number of detected aneurysms by 9.3% (from 258 to 282). Aneurysm-based analysis revealed that the apparent sensitivity of the radiologists' diagnoses made without and with the detection system was 64% and 69%, respectively. The detection system presented 82% of the aneurysms. The detection system more frequently benefited radiologists than being detrimental.
Routine integration of computer-assisted detection with MR angiography for cerebral aneurysms is feasible, and radiologists can detect a number of additional cerebral aneurysms by using the detection system without a substantial decrease in their specificity. The low confidence of radiologists in the system may limit its usefulness.
Diabetes mellitus (DM) is a chronic metabolic disease characterised by hyperglycaemia and glucose intolerance caused by impaired insulin action and/or defective insulin secretion. Long-term ...hyperglycaemia leads to various structural and functional microvascular changes within multiple tissues, including the brain, which involves blood-brain barrier alteration, inflammation and neuronal dysfunction. We have shown previously that drag-reducing polymers (DRP) improve microcirculation and tissue oxygen supply, thereby reducing neurologic impairment in different rat models of brain injury. We hypothesised that DRP could improve cerebral and skin microcirculation in the situation of progressive microangiopathies associated with diabetes using a mouse model of diabetes mellitus. Diabetes was induced in C57BL/6 J mice with five daily consecutive intraperitoneal injections of streptozotocin (50 mg/kg/day). Animals with plasma glucose concentrations greater than 250 mg/dL were considered diabetic and were used in the study following four months of diabetes. DRP (2 ppm) was injected biweekly during the last two weeks of the experiment. Cortical and skin (ear) microvascular cerebral blood flow (mCBF) and tissue oxygen supply (NADH) were measured by two-photon laser scanning microscopy (2PLSM). Cerebrovascular reactivity (CVR) was evaluated by measuring changes in arteriolar diameters and NADH (tissue oxygen supply) during the hypercapnia test. Transient hypercapnia was induced by a 60-second increase of CO
concentration in the inhalation mixture from 0% to 10%. Compared to non-diabetic animals, diabetic mice had a significant reduction in the density of functioning capillaries per mm
(787 ± 52 vs. 449 ± 25), the linear velocity of blood flow (1.2 ± 0.31 vs. 0.54 ± 0.21 mm/sec), and the tissue oxygen supply (p < 0.05) in both brain and skin. DRP treatment was associated with a 50% increase in all three parameters (p < 0.05). According to the hypercapnia test, CVR was impaired in both diabetic groups but more preserved in DRP mice (p < 0.05). Our study in a diabetic mouse model has demonstrated the efficacy of hemorheological modulation of blood flow by DRP to achieve increased microcirculatory flows and tissue oxygen supply.
To understand basic electric properties of nano-sized magnesium oxide (MgO) / low-density polyethylene (LDPE) nanocomposite under DC voltage application, the volume resistivity, the space charge ...distribution and the breakdown strength were investigated. By the addition of nano-sized MgO filler, both the DC breakdown strength and the volume resistivity of LDPE increased. At the average DC electric field of about 85 kV/mm and more, a positive packet space charge was observed in LDPE without MgO nano-filler, whereas a little homogeneous space charge was observed in MgO/LDPE nanocomposite material at the front of electrode. From these results, it is confirmed that the addition of MgO nano-filler leads to the improvement of DC electrical insulating properties of LDPE.
High intracranial pressure (ICP) can be induced by stroke, brain trauma, and brain tumor, and lead to cerebral injury. Monitoring the blood flow of a damaged brain is important for detecting ...intracranial lesions. Blood sampling is a better way to monitor changes in brain oxygen and blood flow than computed tomography perfusion and magnetic resonance imaging. This article describes how to take blood samples from the transverse sinus in a high ICP rat model. Also, it compares the blood samples from the transverse sinus and femoral artery/vein through blood gas analysis and neuronal cell staining. The findings may be of significance to the monitoring of the oxygen and blood flow of intracranial lesions.
Drought has become widespread in the Northern Hemisphere and has affected the specific Mongolian steppes both quantitatively and qualitatively. To simulate vegetation responses to drought, we ...conducted a drought experiment in the Mongolian steppe during a rainy summer growing season. A 30
×
30
m rain shelter excluded natural precipitation during the 2005-growing season, simulating a drought with a return interval of 60–80 years. We examined the effects of the drought on aboveground phytomass (AGP) of each species, total belowground phytomass (BGP), and soil water. The drought drastically reduced AGP and soil water but did not substantially affect BGP. AGP recovered quickly in the late summer of 2006, likely because BGP (which was several times AGP) was not severely damaged by the drought. However, the poorly resilient species did not recover to pre-drought levels, suggesting that the response time scales differed among species. Despite the intense drought, the large root system provided a basis for quick recovery of AGP to pre-drought levels without a shift to a drier equilibrium community. We propose new drought sensitivity and resiliency indices to measure the ecosystem's sustainability and identify species with low sensitivity (i.e., high drought tolerance) that form the baseline of AGP.
Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble ...drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood–brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.
Alzheimer's disease (AD) is a consequence of complex interactions of age-related neurodegeneration and vascular-associated pathologies, affecting more than 44 million people worldwide. For the last ...decade, it has been suggested that chronic brain hypoperfusion and consequent hypoxia play a direct role in the pathogenesis of AD. However, current treatments of AD have not focused on restoring or improving microvascular perfusion. In a previous study, we showed that drag reducing polymers (DRP) enhance cerebral blood flow and tissue oxygenation. We hypothesised that haemorheologic enhancement of cerebral perfusion by DRP would be useful for treating Alzheimer's disease. We used double transgenic B6C3-Tg(APPswe, PSEN1dE9) 85Dbo/Mmjax AD mice. DRP or vehicle (saline) was i.v. injected every week starting at four months of age till 12 months of age (10 mice/group). In-vivo 2-photon laser scanning microscopy was used to evaluate amyloid plaques development, cerebral microcirculation, and tissue oxygen supply/metabolic status (NADH autofluorescence). The imaging sessions were repeated once a month till 12 months of age. Statistical analyses were done by independent Student's t-test or Kolmogorov-Smirnov tests where appropriate. Differences between groups and time were determined using a two-way repeated measures ANOVA analysis for multiple comparisons and post hoc testing using the Mann-Whitney U test. In the vehicle group, numerous plaques completely formed in the cortex by nine months of age. The development of plaques accumulation was accompanied by cerebral microcirculation disturbances, reduction in tissue oxygen supply and metabolic impairment (NADH increase). DRP mitigated microcirculation and tissue oxygen supply reduction - microvascular perfusion was 29.5 ± 5%, and tissue oxygen supply was 22 ± 4% higher than in the vehicle group (p < 0.05). In the DRP group, amyloid plaques deposition was substantially less than in the vehicle group (p < 0.05). Thus, rheological enhancement of blood flow by DRP is associated with reduced rate of beta amyloid plaques deposition in AD mice.
Recently, we showed that decreasing cerebral perfusion pressure (CPP) from 70 mm Hg to 50 mm Hg and 30 mm Hg by increasing intracranial pressure (ICP) with a fluid reservoir induces a transition from ...capillary (CAP) to microvascular shunt (MVS) flow in the uninjured rat brain. This transition was associated with tissue hypoxia, increased blood-brain barrier (BBB) permeability, and brain edema. Our aim was to determine whether an increase in CPP would attenuate the transition to MVS flow at high ICP.
Rats were subjected to progressive, step-wise increases in ICP of up to 60 mm Hg by an artificial cerebrospinal fluid reservoir connected to the cisterna magna. CPP was maintained at 50, 60, 70, or 80 mm Hg by intravenous dopamine infusion. Microvascular red blood cell flow velocity, BBB integrity (fluorescein dye extravasation), and tissue oxygenation (nicotinamide adenine dinucleotide) were measured by in vivo 2-photon laser scanning microscopy. Doppler cortical flux, rectal and cranial temperatures, ICP, arterial blood pressure, and gases were monitored.
The CAP/MVS ratio increased (P<0.05) at higher ICP as CPP was increased from 50 to 80 mm Hg. At an ICP of 30 mm Hg and CPP of 50 mm Hg, the CAP/MVS ratio was 0.6±0.1. At CPP of 60, 70, and 80 mm Hg, the ratio increased to 0.9±0.1, 1.4±0.1, and 1.9±0.1, respectively (mean±SEM; P<0.05). BBB opening and increase of reduced form of nicotinamide adenine dinucleotide occurred at higher ICP as CPP was increased.
Increasing CPP at high ICP attenuates the transition from CAP to MVS flow, development of tissue hypoxia, and increased BBB permeability.
A review in 2020 6 evaluated preclinical and phase 1–3 clinical trials using an inverted funnel statistical method to identify the frequency of unpublished reports and publication bias, and ...concluded, “Pivotal study design differences between experimental studies and clinical trials, including different primary end points and time to treatment, publication bias, neglected quality criteria and low power, contribute to the decline in efficacy in stroke treatments from experimental studies to phase 3 clinical trials.” Justification for the SPAN initiative is that “Unlike most preclinical studies, randomized clinical trials, the gold standard in clinical drug development, require large sample sizes, randomization, proper controls such as a placebo, blinded assessment of outcomes, and stringent data analysis and reporting” 9. Qualification for Thrombolysis and Endovascular Arterial Thrombectomy Intervention in AIS Neuroprotection clinical trials in AIS in animals and their evaluation in clinical trials evolved over decades in parallel with the development of Food and Drug Administration (FDA)–approved recombinant tissue plasminogen activator (rTPA) thrombolysis and endovascular arterial thrombectomy (EAT) treatments. EAT and rTPA thrombolysis imaging guidelines were established in the DEFUSE3 17 study including proximal middle cerebral artery or internal carotid artery occlusion, infarct size of < 70 ml, and a PWI/DWI volume ratio of 1.8 or more.
Purpose: Our previous computer models suggested that intraluminal thrombus (ILT) within an abdominal aortic aneurysm (AAA) attenuates oxygen diffusion to the AAA wall, possibly causing localized ...hypoxia and contributing to wall weakening. The purpose of this work was to investigate this possibility. Methods: In one arm of this study, patients with AAA were placed in one of two groups: (1) those with an ILT of 4-mm or greater thickness on the anterior surface or (2) those with little (< 4 mm) or no ILT at this site. During surgical resection but before aortic cross-clamping, a needle-type polarographic partial pressure of oxygen (Po2) electrode was inserted into the wall of the exposed AAA, and the Po2 was measured. The probe was advanced, and measurements were made midway through the thrombus and in the lumen. Mural and mid-ILT Po2 measurements were normalized by the intraluminal Po2 measurement to account for patient variability. In the second arm of this study, two AAA wall specimens were obtained from two different sites of the same aneurysm at the time of surgical resection: group I specimens had thick adherent ILT, and group II specimens had thinner or no adherent ILT. Nonaneurysmal tissue was also obtained from the infrarenal aorta of organ donors. Specimens were subjected to histologic, immunohistochemical, and tensile strength analyses to provide data on degree of inflammation (% area inflammatory cells), neovascularization (number of capillaries per high-power field), and tensile strength (peak attainable load). Additional specimens were subjected to Western blotting and immunohistochemistry for qualitative evaluation of expression of the cellular hypoxia marker oxygen-regulated protein. Results: The Po2 measured within the AAA wall in group I (n = 4) and group II (n = 7) patients was 18% ± 9% luminal value versus 60% ± 6% (mean ± SEM; P <.01). The normalized Po2 within the ILT of group I patients was 39% ± 10% (P =.08 with respect to the group I wall value). Group I tissue specimens showed greater inflammation (P <.05) compared with both group II specimens and nonaneurysmal tissue: 2.9% ± 0.6% area (n = 7) versus 1.7% ± 0.3% area (n = 7) versus 0.2% ± 0.1% area (n = 3), respectively. We found similar differences for neovascularization (number of vessels/high-power field), but only group I versus control was significantly different (P <.05): 16.9 ± 1.6 (n = 7) vs 13.0 ± 2.3 (n = 7) vs 8.7 ± 2.0 (n = 3), respectively. Both Western blotting and immunohistochemistry results suggest that oxygen-regulated protein is more abundantly expressed in group I versus group II specimens. Tensile strength of group I specimens was significantly less (P <.05) than that for group II specimens: 138 ± 19 N/cm2 (n = 7) versus 216 ± 34 N/cm2 (n = 7), respectively. Conclusion: Our results suggest that localized hypoxia occurs in regions of thicker ILT in AAA. This may lead to increased, localized mural neovascularization and inflammation, as well as regional wall weakening. We conclude that ILT may play an important role in the pathology and natural history of AAA. (J Vasc Surg 2001;34:291-9.)
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