Changes In Vascular Perfusion Research Articles

Optical Coherence Tomography Angiography in Diabetic Patients: A Systematic Review.

Background: Diabetic retinopathy (DR) is the leading cause of legal blindness in the working population in developed countries. Optical coherence tomography (OCT) angiography (OCTA) has risen as an essential tool in the diagnosis and control of diabetic patients, with and without DR, allowing visualisation of the retinal and choroidal microvasculature, their qualitative and quantitative changes, the progression of vascular disease, quantification of ischaemic areas, and the detection of preclinical changes. The aim of this article is to analyse the current applications of OCTA and provide an updated overview of them in the evaluation of DR. Methods: A systematic literature search was performed in PubMed and Embase, including the keywords “OCTA” OR “OCT angiography” OR “optical coherence tomography angiography” AND “diabetes” OR “diabetes mellitus” OR “diabetic retinopathy” OR “diabetic maculopathy” OR “diabetic macular oedema” OR “diabetic macular ischaemia”. Of the 1456 studies initially identified, 107 studies were screened after duplication, and those articles that did not meet the selection criteria were removed. Finally, after looking for missing data, we included 135 studies in this review. Results: We present the common and distinctive findings in the analysed papers after the literature search including the diagnostic use of OCTA in diabetes mellitus (DM) patients. We describe previous findings in retinal vascularization, including microaneurysms, foveal avascular zone (FAZ) changes in both size and morphology, changes in vascular perfusion, the appearance of retinal microvascular abnormalities or new vessels, and diabetic macular oedema (DME) and the use of deep learning technology applied to this disease. Conclusion: OCTA findings enable the diagnosis and follow-up of DM patients, including those with no detectable lesions with other devices. The evaluation of retinal and choroidal plexuses using OCTA is a fundamental tool for the diagnosis and prognosis of DR.

Quantitative Optical Coherence Tomography Angiography Detects Retinal Perfusion Changes in Carotid Artery Stenosis.

BackgroundCarotid artery stenosis (CAS) is a multifaceted disease characterized by possible ocular involvement. Treatment with carotid endarterectomy helps to restore cerebral perfusion, which may prevent ocular and cerebral complications. The main aim was to assess retinal and choroidal vascular perfusion changes before and after endarterectomy in patients affected by CAS.MethodsThe design of the study was prospective and observational, including patients affected by CAS and healthy controls. The follow-up was 3 months. We performed quantitative optical coherence tomography (OCT) angiography (OCTA) analyses of retinal perfusion changes, before and after endarterectomy. The main outcome measures were the quantitative changes of choroidal thickness (CT), retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL); vessel density (VD); and vessel tortuosity (VT) OCTA metrics were also measured.ResultsSixty eyes of 30 patients affected by CAS and 30 eyes of 30 controls were included. We separately considered the ipsilateral eyes to CAS, the contralateral eyes to CAS, and the healthy eyes. Visual symptoms were absent in all the patients. RNFL and GCL resulted similar between patients and controls (p > 0.05). CT was significantly thinner in ipsilateral eyes than controls (p < 0.01), and it resulted unchanged after surgery (p > 0.05). VD resulted significantly altered only in some plexa of the ipsilateral eyes (p < 0.01), whereas VT disclosed decreased values of the entire retinal vascular network, both in ipsilateral and contralateral eyes (p < 0.05). Endarterectomy was followed by statistically significant improvement of retinal perfusion (p < 0.05).ConclusionOptical coherence tomography angiography can noninvasively detect postendarterectomy retinal perfusion improvements in CAS patients with baseline diabetes and hypertension as a systemic risk factor.

OCT-Angiography as a reliable prognostic tool in laser-treated proliferative diabetic retinopathy: The RENOCTA Study.

To quantitatively assess retinal neovascularizations (RNVs) in proliferative diabetic retinopathy (PDR) before and after photocoagulative laser treatment (PLT) using Optical Coherence Tomography Angiography (OCT-A). Consecutive patients with PDR were examined with fluorescein angiography (FA) and OCT-A before and after PLT. Baseline and after-treatment FA images were quantitatively analyzed to assess both the RNVs area and leakage area. On OCT-A RNVs area, vascular perfusion density (VPD), vessel length density (VLD) and fractal dimension were computed. VPD of the full-retina OCT-A underneath the RNV was determined to evaluate potential laser-induced changes in vascular perfusion. Fifteen eyes of 13 patients with PDR were enrolled. The mean area of the RNVs was 0.47 ± 0.50 mm2 in the baseline OCT-A and 0.32 ± 0.40 mm2 in the post-treatment assessment (p = 0.0002). The mean RNV VPD of RNV was 2% ± 4% in pre-treatment and 1% ± 1% for the post-treatment (p = 0.0001). The mean VLD of RNV was 7.26 ± 1.53 at baseline and 6.64 ± 1.65 in the post treatment (p = 0.0002). A significant difference in terms of mean RNVs area and VPD reduction between eyes that needed additional treatment and those that did not (~40% vs ~20%; p < 0.05), was observed. Mean VPD of full-retinal thickness OCT-angiogram was 55% ± 10% for the pre-treatment and 53% ± 8% for the post treatment scan (p = 0.02). The quantitative OCT-A assessment of laser-induced changes of RNVs can be a useful non-invasive approach for determining treatment efficacy. A reduction of RNVs area or VPD ⩾ 40% might reveal those eyes that won't require additional treatment. Retinal perfusion impairment seemed to progress independently from the treatment.

Abstract No. 528 Antivascular ultrasound (AVUS) demonstrates vascular disruption in a dose-dependent manner in a DEN rat model of hepatocellular carcinoma

Previous studies have shown low-intensity ultrasound used with intravascular microbubbles (uB) disrupts tumor neovasculature. This study aims to evaluate changes in vascular perfusion following antivascular ultrasound (AVUS) therapy in a translational rat model of hepatocellular carcinoma (HCC). HCC was induced in 6 Wistar rats via diethylnitrosamine (DEN) ingested in drinking water for 12 weeks. Rats received AVUS therapy at low and high doses. The low dose group (n = 3) was treated at 1 W/cm2 for 1 min with 0.2 mL perflutren lipid microspheres (microbubbles, uB) injected IV. The high dose group (n = 3) was treated at 2 W/cm2 for 2 min with 0.7 mL IV uB. Perfusion was assessed by nonlinear contrast (NLC) and power Doppler (PD) ultrasound imaging before and after therapy. From each imaging mode, peak enhancement (PE) and perfusion index (PI) were measured. Histologic analysis of H&E and trichrome sections was performed after natural death or euthanasia. In the high-dose group, perfusional measures of PE (PD) decreased by 32.1% on average, and PI decreased 29.3% following AVUS therapy. NLC showed similar decreases: reduction in PE by 42.9% and PI by 44.8%. Histopathologic correlation showed hemorrhagic necrosis covering 61.5% of tumors’ cross-sectional area. In contrast, the low-dose group showed only modest changes in perfusion, and on average showed slight increases in perfusional measures (PE and PI). PD showed an average increase of 4.5% and 6.9% in PE and PI, respectively. NLC similarly showed average increases of 1.3% and 54.9% in PE and PI, respectively. Histologically, the low dose group showed less severe hemorrhagic necrosis in only 19.5% tumor cross sectional area. High-dose AVUS showed decreased perfusion and increased hemorrhagic necrosis on US and histology, while changes were less severe with low-dose AVUS. These dose-dependent effects are now being investigated in our translational model of HCC to further refine this novel, image-guided interventional therapy.Tabled 1Max Dose uB%Hemorrhage on Tumor Cross-Sections (SEM)PE (PD) Decrease Avg (%) (SEM)PI (PD) Decrease Avg (%) (SEM)PE (NLC) Decrease Avg (%) (SEM)PI (NLC) Decrease Avg (%) (SEM)High-dose group0.7mL61.5 (10.6)32.1 (15.2)29.3 (17.0)42.9 (18.2)44.8 (14.4)Low-dose group0.3mL19.5 (9.6)-4.5 (6.7)-6.9 (13.7)-1.3 (13.0)-54.9 (21.1) Open table in a new tab

Stem cells enhance reperfusion following ischemia: Validation using laser speckle imaging in predicting tissue repair.

The lack of real-time assessment of vascular perfusion changes remains a major weakness in assessing the efficacy of bone marrow stromal cells (BMSC) therapeutic ischemia reperfusion (I/R) injury. This study provides for the first time the real-time in vivo perfusion monitoring in I/R mice with BMSC therapy. Animal model. Surgically created cutaneous flaps perfused by the inferior epigastric vessels were subjected to 3.5 hours of ischemia/reperfusion. Wound healing and vascular perfusion were assessed by Image-J and laser speckle contrast analysis (LSCA) in three groups (sham, I/R, and I/R + BMSC). BMSC tracking was quantified in an additional two groups (with/without I/R) using intravital fluorescent microscopy. The histopathology of skin flaps was examined by hematoxylin and eosin stain. Infiltrated macrophages were analyzed by confocal immunofluorescent microscopy. Postischemic tissues treated with BMSC demonstrated significantly greater survival than I/R control. On days 3 to 7 postreperfusion, both proximal and distal areas in BMSC-treated flaps demonstrated greater levels of perfusion than untreated I/R flaps (P < 0.05). Intravital fluorescent microscopy revealed that numbers of labeled BMSC were significantly increased in the distal area compared to the proximal area in both with and without ischemic mice. Histological examination showed lower necrosis and infiltrated inflammatory cells in I/R + BMSC-treated mice versus I/R controls. BMSC accumulated in I/R flaps and exerted beneficial effects including: 1) improving vascular perfusion and 2) attenuating inflammatory cell infiltration. LSCA facilitates monitoring of the real-time restitution of perfusion during flap wound healing in experimental animals and could also similarly applied in clinical investigations. NA. Laryngoscope, 128:E198-E205, 2018.

Vascular Remodeling Underlies Re-Bleeding in Hemophilic Arthropathy

Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. To better understand these mechanisms, we investigated the time course of synovial, vascular, stromal and cartilage changes in response to a single induced hemarthrosis in FVIII-deficient mice, compared the observed changes in vascular architecture to the changes in mouse models of rheumatoid arthritis (RA) and osteoarthritis (OA), and explored the extent to which these findings correlated with the development of hemophilic arthropathy in patients. Following a single induced hemarthrosis in the FVIII-deficient mouse, we found soft tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture in the injured joint. While soft tissue changes were rapidly reversible, and cartilage changes were mild and mostly reversible, ongoing structural changes of abnormal vascularity persisted for months. These vascular changes involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105) and vascular endothelial growth factor (VEGF), as well as altered joint perfusion as determined by in vivo imaging. Surprisingly, these vascular changes were also seen in uninjured joints, suggesting systemic mediation of the observed effects. Changes in vascular architecture and pronounced expression of α-SMA were unique to hemophilia, and were not found in joint tissue obtained from RA or OA mice or from tissue from patients with OA or RA. Since FVIII-deficient mice do not suffer from spontaneous joint bleeding, human studies needed to be designed to reveal if such vascular changes were associated with joint bleeding and joint deterioration. Therefore, to determine if vascular perfusion changes were also present in hemophilia patients and to what extent they were related with joint bleeding and the degree of arthropathy, a cohort of 26 adult patients with hemophilia was studied prospectively. Radiographic Pettersson Scores and clinical Hemophilia Joint Health Scores (HJHS) were assessed and joint bleed status and vascularity changes were investigated by dynamic in vivo imaging using power Doppler (PD) during high resolution musculoskeletal ultrasound examinations of 156 joints (both elbows, knees and ankles of each patient) at baseline and, subsequently of 10 joints during painful episodes. Subclinical joint bleeding was present in 41% of joints at baseline. Positive PD signals were more frequently present in joints with subclinical bleeding than in joints without (83% vs. 55%; p< 0.01), while the mean PD signal score was significantly higher in bleeding joints (3.1 vs. 1.5; p < 0.01). Importantly, joint bleed status was independently associated with PD signal score (odds ratio [OR] = 1.45 [95% CI: 1.13, 1.86, p = 0.0035]) and with Pettersson score (OR = 1.21 [95%CI: 1.03, 1.43, p = 0.0185]) after adjusting for HJHS. Acute bleeding episodes, irrespective of occurring in previously non-bleeding or in previously subclinically bleeding joints only happened in joints where vascularity changes were present at baseline. Moreover, during these episodes, mean PD signal increased significantly from 3.5 at baseline to 6.0 (maximum 9 per joint; p≤0.05). Therefore, in vivo imaging demonstrated that those vascular changes, first observed in the FVIII-deficient mouse, were significantly associated with bleeding and joint deterioration in hemophilia patients.In aggregate, our observations in hemophilic mice and patients provide strong evidence that abnormal blood vessel formation and dynamic vascular remodeling facilitate and perpetuate joint bleeding in response to local and/or systemic stimuli. While changes in vascularity appear to be an important link to repeated bleeding and progression of arthropathy, the interrelations of bleeding and vascular changes are complicated and will require further study. These findings not only provide new insights into the pathobiology of progression of hemophilic arthroapthy, but also open new avenues to study molecular targets for angiogenesis inhibition to prevent aberrant vessel formation, potentially increasing the effectiveness of clotting factor replacement therapy. DisclosuresVon Drygalski:CSL Behring: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Research Funding; Biogen: Honoraria, Research Funding; Hematherix Inc: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Research Funding; Pfizer: Honoraria; Baxalta: Honoraria, Research Funding. Mosnier:Hematherix Inc: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Contrast-enhanced ultrasound reveals real-time spatial changes in vascular perfusion during early implantation in the macaque uterus

To use contrast-enhanced ultrasound (CEU) to quantify blood flow in the macaque uterus during early pregnancy. Prospective nonhuman primate study. Oregon National Primate Research Center. Naturally cycling female rhesus macaques (Macaca mulatta). Female macaques were mated on days 11-14 of the cycle. Females were then imaged by CEU and Doppler ultrasound once every 3 days from day 21 through day 39 of the fertile cycle. Visualization and quantification of uterine vascular perfusion. CEU identified the primary placental disc and underlying vessels approximately 2 days earlier than Doppler ultrasound was able to observe endometrial thickening. CEU revealed spatial differences in vascular perfusion between the endometrium, myometrium, and endometrial-myometrial (junctional) zone. Myometrium displayed the highest rate of blood flow (>10 mL/min/g tissue). There was less blood flow in the endometrium and junctional zone (<3 mL/min/g). A brief fall in progesterone was observed during early implantation, which was correlated with reduced blood flow to all three uterine compartments, but did not reduce flow to the placenta. CEU provides a sensitive, noninvasive method to assess vascular perfusion of the uterus during embryo implantation in macaques. We propose CEU as a new diagnostic tool to monitor vascular changes associated with early pregnancy in women.

Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease

Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor rim was significantly higher than that in the controls. HBF, HBV, HAI, HAP and HPP, but not MTT and PS, were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.

Contrast-Enhanced Ultrasound Reveals Real-Time Temporospatial Changes in Uterine and Placental Vascular Perfusion During Early Pregnancy in Rhesus Macaques.

Classical morphological studies on preserved uterine tissue sections have provided an anatomical understanding of the uterine vascular changes that occur during early pregnancy, but little is known regarding the physiological changes (i.e. uterine blood flow) that occur in vivo during pregnancy initiation in primates. Doppler ultrasound (DUS), the prevailing technique used to detect the fetal heartbeat, lacks the sensitivity needed to measure the low velocity vascular perfusion associated with implantation and subsequent early placentation. Contrast-enhanced ultrasound (CEU) is a non-invasive method with high spatial resolution used to assess quantitative differences in vascular blood flow and volume. Thus, the goals of this study were to use CEU to characterize and quantify the temporal changes in the vascular adaptations associated with early pregnancy, and to compare the information provided by CEU and DUS. Adult female rhesus macaques (n = 5) in the time-mated breeding program at ONPRC were pair-caged with males of proven fertility for 96 hr during the window of ovulation, and mating was confirmed by video recording. DUS and CEU began 14 days after the first day of pairing (DAP) and continued every 3 days until a fetal heartbeat was detected by DUS. The uterus of sedated animals was first visualized on a Voluson Expert 730 system (GE HealthCare) with a 2D trans-abdominal probe with Doppler capability. CEU was performed with a contrast-specific imaging technique, via an Acuson Sequoia system (Siemens), during a continuous intravenous infusion of lipid microbubble contrast reagent (Definity). Vascular blood flow and blood volume were quantified for the myometrium, endometrium and placental lobes from replenishment kinetics on the intensity data obtained after a high power pulse sequence destroyed all microbubbles in the acoustical beam. A functional corpus luteum formed (P4 > 4 ng/mL) in all females and 80% (4/5) became pregnant, as confirmed by a fetal heartbeat observed on 28.0±1.2 DAP. CEU clearly delineated the primary and secondary lobes of the placenta ~2 days apart (paired t-test; P<0.05), on 19.8±1.0 and 22.0±1.2 DAP, respectively. DUS was not able to differentiate between the placental lobes and detected endometrial thickening on 22.8±1.0 DAP, 3 days after (P<0.05) CEU identified the primary placental lobe. Visualization of the primary lobe correlated with the vaginal bleeding associated with implantation. The CEU calculated vascular perfusion was greater (P<0.05) in the primary placental lobe, which exhibited a 29% increase in relative blood volume and a 40% increase in relative blood flow, compared with the secondary lobe on the day of heartbeat detection. CEU identified greater flow through the hypertrophied endometrial spiral arteries supplying the placental lobes compared with other regions of the endometrium, whereas changes in the myometrium were not seen. In sum, CEU has defined the temporospatial changes in vascular perfusion associated with the anatomical vascular remodeling during early pregnancy in primates. Thus, CEU has great potential as a tool for basic researchers examining the peri-implantation period in the primate endometrium. Furthermore, CEU has promise as a future application for obstetricians, to resolve vascular complications that arise during pregnancy, including ectopic implantation and preeclampsia. Supported by NIH grants HD055744, HD18185, HD07133 and RR000163. (platform)

Changes in Vascular Perfusion of the Endometrium in Association with Changes in Location of the Embryonic Vesicle in Mares1

The equine embryonic vesicle is mobile on Days 12-14 (Day 0 = ovulation), when it is approximately 9-15 mm in diameter. Movement from one uterine horn to another occurs, on average, approximately 0.5 times per hour. Mobility ceases (fixation) on Days 15-17. Transrectal color Doppler ultrasonography was used to study the relationship of embryo mobility (experiment 1) and fixation (experiment 2) to endometrial vascular perfusion. In experiment 1, mares were bred and examined daily from Day 1 to Day 16 and were assigned, retrospectively, to a group in which an embryo was detected (pregnant mares; n = 16) or not detected (n = 8) by Day 12. Endometrial vascularity (scored 1-4, for none to maximal, respectively) did not differ on Days 1-8 between groups or between the sides with and without the corpus luteum. Endometrial vascularity scores were higher (P < 0.05) on Days 12-16 in both horns of pregnant mares compared to mares with no embryo. In pregnant mares, the scores increased (P < 0.05) between Day 10 and Day 12 in the horn with the embryo and were higher (P < 0.05) than scores in the opposite horn on Days 12-15. In experiment 2, 14 pregnant mares were examined from Day 13 to 6 days after fixation. Endometrial vascularity scores and number of colored pixels per cross-section of endometrium were greater (P < 0.05) in the endometrium surrounding the fixed vesicle than in the middle portion of the horn of fixation. Results supported the hypothesis that transient changes in endometrial vascular perfusion accompany the embryonic vesicle as the vesicle changes location during embryo mobility.

“Growing pains” in children are not associated with changes in vascular perfusion patterns in painful regions

The most common cause of recurring childhood musculoskeletal pain is termed "growing pains" (GP). The etiology and pathogenesis are unknown. There is an increased prevalence of migraine headaches in families with children with GP. This fact, and the sudden onset and severity of GP episodes, has led to speculation that GP may have a vascular component. Therefore, we investigated whether GP are associated with vascular perfusion changes, measured by technetium-99 methylene diphosphate (MDP) bone scintigraphy. Eleven patients with GP who underwent technetium-99 MDP bone scans were compared to 12 children who underwent bone scans for other indications. The uptake in the blood pool phase, static images, and blood pool phase/static image ratio were measured in the right mid-tibia region (painful among patients with GP) and right mid-femur (non-painful). Student's t-test was used to compare these measurements at painful and painless regions among GP children, and to compare children with or without GP. There were no significant differences between children with GP and without GP in the blood pool, static images, and blood pool/static images in all localities. There were also no significant differences among patients with GP between painful regions and non-painful regions. We conclude that GP are not associated with vascular perfusion changes in painful regions as opposed to migraine headaches.

Mesenteric afferent nerves are sensitive to vascular perfusion in a novel preparation of rat ileum in vitro.

Using novel in vitro preparations of vascularly perfused rat ileum, we investigated mesenteric afferent sensitivity to vascular perfusion. Gut (GPP) and vascular (VPP) perfusion pressures were recorded simultaneously with afferent discharge (AD). After preconstriction (L-phenylephrine), capsaicin (100 microM, gut lumen) caused a transient increase in AD and a sustained fall in VPP, supporting afferent modulation of vascular tone. In turn, AD was affected by vascular perfusion rate (VPR). Increasing VPR step-wise (0.6 to 1.0, 1.4 and 1.8 ml/min) caused concomitant falls in AD, returning at 0.6 ml/min. Terminating flow (5 min) increased AD. Afferent responses were independent of changes in GPP, vascular O2, or the gut "tube" ("gut-off"). In gut-off studies, where capsaicin (100 nM ia) still reduced VPP, flow-associated falls in AD were abolished by the enzyme neuraminidase (0.2 U/ml ia or extravascularly over 20 min). In contrast, increased AD after stopped flow was unaffected. We propose that mesenteric afferents "sense" changes in vascular perfusion. The precise stimuli (pressure and/or flow) and the physiological relevance to control of local circulation remain to be determined.

Vascular responses in the skin: an accessible model of inflammation.

The skin is the most accessible organ of the human body in which to study the inflammatory process. Until recently, changes in vascular perfusion and permeability could only be superficially visualized. A novel combination of techniques has now provided the appropriate tools with which to study this more extensively in humans.

SPECT and neuropsychological performance in severe depression treated with ECT

Background: In severe depression, studies of regional cerebral blood flow (rCBF) by SPECT have not produced uniform results. The association between changes in SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No data are available on benzodiazepine receptor function SPECT studies in ECT. Methods: Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria for major depression were studied by SPECT (rCBF by relative ECD uptake in all, and benzodiazepine receptor function by iomazenil uptake in five subjects) before and 1 week after clinically successful bitemporal ECT. Clinical and neuropsychological test scores were used as references for the possible changes in SPECT. Results: An increased perfusion after ECT was observed in right temporal and bilateral parietal cortices, whereas no reductions in relative ECD uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant increase in the benzodiazepine receptor uptake in all studied cortical regions except temporal cortices. Conclusions: Clinically successful ECT was associated with changes in vascular perfusion and GABAergic neurotransmission, providing new evidence for the mechanism of action of ECT and for the neurobiology of severe drug-resistant depression.

A focusing image probe for assessing neural activity in vivo

We describe a compact, focusing image probe to record rapid optical changes from neural tissue. A gradient index (GRIN) lens served as a relay lens from tissue to a microscope objective which projected an image onto a CCD camera. The microscope objective and camera assembly was adjusted independently from the GRIN lens, allowing focus changes without disturbing the probe/tissue interface; firm contact minimized movement and specular reflectance. Fiber optics around the probe perimeter provided diffuse illumination from a 780 nm laser, or 660 and 560 nm light emitting diodes. To characterize depth-of-field, we imaged a black suture through increasing tissue thicknesses. Light modulation by the suture remained detectable down to 900 μm using 780 nm illumination. We acquired images from cardiorespiratory areas of the rat dorsal medulla, at different depths and illumination wavelengths. Images illuminated at 560 nm were dominated by vasculature flow patterns, while 660 nm illumination revealed different spatial patterns which preceded vascular flow by 40 ms and may represent cardiac-related neural activity. Using 780 nm light, image sequences triggered by the cardiac R-wave showed vascular perfusion changes with delayed and broader responses at deeper levels. Electrical stimulation within the vagal bundle caused fast optical changes which track the electrical response, with a different spatial distribution from hemodynamic signals.

Mechanisms for Vasopressin Effects on Intraocular Pressure in Anesthetized Rats

Continuous intracameral infusions of a balanced salt solution (0.175 μl min−1) have been reported to raise intraocular pressure (IOP) in anesthetized rats. Palm et al. (1995) previously reported that this effect was attenuated significantly by inclusion of arginine-vasopressin (AVP, 10 ng 0.175 μl−1) in the infusate. This study used experimental and computer simulation methods to investigate factors underlying these changes in IOP. First, constant intracameral infusions of artificial cerebrospinal fluid (aCSF) at different fixed rates (0.049–0.35 μl min−1) were used to estimate the outflow resistance. Secondly, IOP responses were measured during an 2 hr intracameral infusion of either aCSF or AVP that was the sum of a small constant component (0.05 μl min−1) and a larger periodic component (0.25 μl min−1, cycling for 4 min on, then 4 min off); the mean infusion rate was 0.175 μl min−1. As shown previously for 0.175 μl min−1constant infusions, the periodic aCSF infusion induced a significant rise in IOP that was attenuated by AVP administration. Complex demodulation analysis and the estimated gain parameter of a second order transfer function fit to the periodic responses indicated that outflow resistance increased significantly during the infusions in both aCSF and AVP groups, but that the indices of resistance did not differ significantly between aCSF and AVP infused eyes. This finding implies that changes in outflow resistance do not explain the difference in IOP responses to intracameral aCSF and AVP. The two responses differed significantly, though, in damping factors, such that the aCSF responses were considerably more underdamped than the AVP responses. It is hypothesized that aCSF-induced increase in IOP reflects both (1) a small component reflecting increased outflow resistance and (2) a larger non-resistive component. Since the non-resistive component is insensitive to pretreatment with acetazolamide, it is suggested that the aCSF-induced elevation in IOP reflects primarily vascular perfusion changes that are reduced by local vasoconstrictor actions of AVP. The latter mechanism likely maintains vascular perfusion of the globe when intraocular hypertension develops.

Cortical and vascular prostaglandin synthesis during renal allograft rejection in the rat.

Alterations in local prostacyclin and thromboxane synthesis could mediate the changes in vascular perfusion and platelet deposition in acutely rejecting renal allografts and prostaglandin E2 (PGE2) has been implicated in the regulation of the immune response. 6-Keto-prostaglandin F1 alpha (6 KetoPGF1 alpha), thromboxane B2 (TxB2) (the stable degradation products of prostacyclin and thromboxane A2 [TxA2], respectively) and PGE2 were measured in incubates of cortical slices taken from rat renal allografts or isografts one to seven days after transplantation. 6 KetoPGF1 alpha and TxB2 synthesis was also measured in incubates of blood vessels supplying and transplanted with the kidney in these animals. During the phase of cellular rejection (3-5 days), TxB2 synthesis was selectively elevated in allografted renal cortex, renal artery, renal vein, and abdominal aorta in comparison with isografted tissues. There was also a small but significant rise in cortical PGE2 synthesis at this time, but vascular and cortical 6 KetoPGF1 alpha production remained unchanged. Renal infarction, occurring 7 days after transplantation, was accompanied by a nonspecific rise in the synthesis of all three prostaglandins by renal cortical slices. Increased tissue TxA2 synthesis may contribute to local thrombosis and decreased graft perfusion during acute rejection, thereby potentiating graft destruction.

Vascular effects of substance P change synaptic responsiveness of cat dorsal horn neurons

The effects of systemically administered substance P were examined on the responses induced by noxious (radiant heat) and non-noxious (air jets) peripheral stimuli in dorsal horn neurons of the feline spinal cord. Substance P produced a significant fall in arterial blood pressure and selectively enhanced responses to noxious heat stimulation. Other vasoactive substances administered systemically caused either selective increases or decreases in noxious heat induced responses which coincided with decreases or increases in systemic arterial blood pressure respectively. It was concluded that the selective neuronal effects of substance P were secondary to changes in vascular perfusion in the area stimulated by the radiant heat source.

Low-Level X-Radiation-Induced Vascular Alterations in Normal and DMBA-Treated, Tumor-Bearing Cheek Pouch Epithelium of Syrian Hamsters

Studies were conducted to examine late changes in vascular volume and vascular perfusion of normal and tumor-bearing Syrian hamster cheek pouches, treated either with DMBA, repeated low-level x radiation, or DMBA + x radiation. Hamsters received once-weekly 20-R exposures to the head and neck for 17 consecutive weeks. During weeks 1 to 5 and 7 to 11 of irradiation, 0.1% DMBA was applied to right cheek pouches twice weekly. Thirty-nine weeks after initial treatment, animals were injected intravenously with /sup 51/Cr-labeled erythrocytes to determine cheek pouch blood volume and /sup 86/RbCl to determine the vascular perfusion of cheek pouch tissues. Following excision of tumors and pouches, /sup 51/Cr and /sup 86/Rb activities and histopathologic changes were assessed. Irradiated animals had no tumors, 53% of the DMBA-treated animals had tumors, and 75% of the DMBA + radiation-treated animals had tumors. Irradiated cheek pouches had increased blood volume, and DMBA-treated tumor-bearing pouches had increased blood volume and perfusion. DMBA + radiation-treated tumor-bearing pouches had increased blood volume similar to that seen in irradiated pouches and increased blood perfusion similar to that seen in DMBA-treated, tumor-bearing pouches. While the presence of DMBA-induced tumors was related to changes in vascular perfusion in all groups,more » low-level x radiation appeared to alter changes in blood volume caused by DMBA or DMBA-induced tumors.« less