Perfusion Volume Research Articles

Pathogenetic Substantiation of Therapeutic and Preventive Measures in Severe Coronavirus Infection

Abstract The basis of coronavirus disease is an infectious process, accompanied by a varying degree of activity of pathological processes. Based on the study of the pathological course of infection, modern approaches to the treatment and prevention of complications of coronavirus infection are presented. The main strategic pathogenetic direction in the creation of effective programs for the treatment of COVID-19, as well as the prevention of fatal complications, should be a set of measures enhancing permissive regulatory influences and events. Endothelium, being a source of inflammatory mediators and a transducer of their regulatory effects on the vascular tone, is involved in the development and alternation of vascular reactions, changing the volume of perfusion. The main mechanism for the development of endothelial dysfunction and damage is associated with an imbalance between the generation of reactive oxygen species and the power of the antioxidant defense system. Any measures to protect the endothelium, reducing the severity of microcirculatory disorders and hypoxia, will have a therapeutic and preventive effect on fatal complications. In this regard, in the treatment of COVID-19, the use of synthetic gas transport preparations based on perfluorocarbon nanodispersed emulsions with a clinical effect directed at once to several patho-genetic links underlying the progression of COVID-19 disease can be quite effective. The necessity of a comprehensive effect on pathogenesis using sanogenetic principles of treatment, allowing influencing the speed and time of onset of resolution of inflammation, which can reduce the number of complications and deaths of the disease, is substantiated.

A Comparative Study Between Clomiphene Citrate and Tamoxifen for induction of Ovulation in Women Complaining of Polycystic Ovary Syndrome

PCOS is the most common endocrine disorder among women between the ages of 18 and 44. It affects approximately 2% to 20% of this age group depending on how it is defined. PCOS is due to a combination of genetic and environmental factors. Objective: To compare the efficacy of Clomiphene citrate and Tamoxifen induction of ovulation women with polycystic ovary syndrome. Patients and Methods: This clinical trial study was conducted at Al-Husien Hospital from June 2019 to December 2019 after approval of the research ethics committee, on 100 patients with P.C.O. The participants were recruited from women attending the outpatient infertility clinic of Al-Husien Hospital.Patients are classified randomly into 2 groups: Group A: 50 patients (clomiphene Group). Group B: 50 patients (tamoxifene Group).Results: Ovulation rate was significantly better under tamoxifen therapy. Pregnancy rate was significantly better under tamoxifen therapy. Number of stimulated follicles was not significantly different between the two drugs.Endometrial thickness was significantly better under tamoxifen therapy both preovulatory and midluteal. Endometrial perfusion volume (EV), Vascularization index (VI), and Vascularization flow index (VFI) were significantly better under tamoxifen therapy. Adverse effects with thetwo drugs were non-significant. Endometrialperfusion indices weresignificantly better pregnant versus non-pregnantcases.Conclusion:Tamoxifen can give similar or even better results than clomiphene citrate induction of ovulation women with PCOS. Each of them can be used as a first line option for induction of ovulation women with PCOS in selected cases.

Testicular perfusion and testicular volume after inguinal hernia repair

Testicular perfusion and testicular volume after inguinal hernia repair

Automatic Diagnosis of Chronic Thromboembolic Pulmonary Hypertension Based on Volumetric Data from SPECT Ventilation and Perfusion Images

Chronic thromboembolic pulmonary hypertension (CTEPH) is confirmed by visual analysis of single-photon emission computer tomography (SPECT) ventilation and perfusion (V/Q) images. Defects in the perfusion image discordant with the ventilation image indicate obstructed segments and the positive diagnosis of CTEPH. A quantitative metric and classification algorithm are proposed based on volumetric data from SPECT V/Q images. The difference in ventilation and perfusion volumes (VV-P) is defined as a quantitative metric to identify discordant defects in the SPECT images. The algorithm was validated with 22 patients grouped according to their diagnosis: (1) CTEPH and (2) respiratory pathology. Volumetric data from SPECT perfusion images was also compared before and after treatment for CTEPH. CTEPH was detected with a sensitivity of 0.67 and specificity of 0.80. The performance of volumetric data from SPECT perfusion images for the evaluation of treatment response was studied for two cases and improvement of pulmonary perfusion was observed in one case. This study uses volumetric data from SPECT V/Q images for the diagnosis of CTEPH and its differentiation from respiratory pathologies. The results indicate that the defined metric is a viable option for a quantitative analysis of SPECT V/Q images.

Therapeutic and rehabilitation complex for the treatment of patients with chronic generalized periodontitis and bruxism

Background. The article discusses modern concepts of the relationship of periodontal disease and bruxism.
 Aim: to study the efficiency of the proposed therapeutic and rehabilitation complex for patients with chronic generalized periodontitis and bruxism.
 Methods. 73 patients aged 3045 years with a diagnosis of chronic generalized periodontitis of moderate severity and bruxism were examined. The control group consisted of 15 apparently healthy individuals of the same age to clarify the functional parameters of the norm. To assess the effectiveness of the proposed therapeutic and rehabilitation complex, clinical, Doppler flowmetric and electromyographic research methods were used.
 Results. High efficiency of the therapeutic and rehabilitation complex in the treatment of chronic generalized moderate periodontitis and bruxism has been revealed. An analysis of changes in time of clinical symptoms revealed that when using this program, which includes basic therapy, laser phoresis, ozone irrigation of the gums, the intake of phyto-complex and local-mineral complexes, the use of dental pins with propolis and phytocomplex, physiotherapy exercises and fluctuorization, positive changes were pronounced. Under the influence of the course effect of therapeutic procedures, patients showed an increase in blood perfusion volume by 37.7% (p 0.05), blood flow perfusion rate by 58.2% (p 0.05) from the initial values. At the same time, a decrease by 51.82% (p 0.05) from the initial indices of bioelectric activity of the temporal muscle at rest was registered, as well as by 40.4% (p 0.05) with voluntary constriction, and a decrease in the bioelectric activity of the mastication muscle at rest by 47.4% (p 0.05), and with voluntary constriction by 35.12% (p 0.05).
 Conclusion. The data obtained based on electromyography and laser Doppler flowmetry indicate that the developed treatment and rehabilitation complex is an effective method for correcting the microcirculation of periodontal vessels, the functional activity of the maxillofacial muscles.

Therapeutic and rehabilitation complex for the treatment of patients with chronic generalized periodontitis and bruxism

Background. The article discusses modern concepts of the relationship of periodontal disease and bruxism.
 Aim: to study the efficiency of the proposed therapeutic and rehabilitation complex for patients with chronic generalized periodontitis and bruxism.
 Methods. 73 patients aged 3045 years with a diagnosis of chronic generalized periodontitis of moderate severity and bruxism were examined. The control group consisted of 15 apparently healthy individuals of the same age to clarify the functional parameters of the norm. To assess the effectiveness of the proposed therapeutic and rehabilitation complex, clinical, Doppler flowmetric and electromyographic research methods were used.
 Results. High efficiency of the therapeutic and rehabilitation complex in the treatment of chronic generalized moderate periodontitis and bruxism has been revealed. An analysis of changes in time of clinical symptoms revealed that when using this program, which includes basic therapy, laser phoresis, ozone irrigation of the gums, the intake of phyto-complex and local-mineral complexes, the use of dental pins with propolis and phytocomplex, physiotherapy exercises and fluctuorization, positive changes were pronounced. Under the influence of the course effect of therapeutic procedures, patients showed an increase in blood perfusion volume by 37.7% (p 0.05), blood flow perfusion rate by 58.2% (p 0.05) from the initial values. At the same time, a decrease by 51.82% (p 0.05) from the initial indices of bioelectric activity of the temporal muscle at rest was registered, as well as by 40.4% (p 0.05) with voluntary constriction, and a decrease in the bioelectric activity of the mastication muscle at rest by 47.4% (p 0.05), and with voluntary constriction by 35.12% (p 0.05).
 Conclusion. The data obtained based on electromyography and laser Doppler flowmetry indicate that the developed treatment and rehabilitation complex is an effective method for correcting the microcirculation of periodontal vessels, the functional activity of the maxillofacial muscles.

Intravoxel incoherent motion diffusion-weighted imaging for discrimination of benign and malignant retropharyngeal nodes.

Anatomical imaging criteria for the diagnosis of malignant head and neck nodes may not always be reliable. This study aimed to evaluate the diagnostic value of conventional diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) DWI in discriminating benign and malignant metastatic retropharyngeal nodes (RPNs). IVIM DWI using 14 b-values was performed on RPNs of 30 patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC) and 30 patients with elevated plasma Epstein-Barr virus (EBV)-DNA without NPC who were part of an EBV-based NPC screening program. Histogram measurements of the two groups were compared for pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion volume fraction (f) and apparent diffusion coefficient (ADC) using the Mann-Whitney U test. Area under the curves (AUCs) of significant measurements were calculated from receiver-operating characteristics analysis and compared using the DeLong test. Compared with metastatic RPNs, benign RPNs had lower ADCmean (0.73 vs 0.82 × 10-3mm2/s) and Dmean (0.60 vs 0.71 × 10-3mm2/s) and a higher D*mean (35.21 vs 28.66 × 10-3mm2/s) (all p < 0.05). There was no difference in the f measurements between the two groups (p = 0.204 to 0.301). Dmean achieved the highest AUC of 0.800, but this was not statistically better than the AUCs of the other parameters (p = 0.148 to 0.991). Benign RPNs in patients with EBV-DNA showed greater restriction of diffusion compared with malignant metastatic RPNs from NPC. IVIM did not show a significant advantage over conventional DWI in discriminating benign and malignant nodes.

Quantification of diabetic macular ischemia using novel three-dimensional optical coherence tomography angiography metrics.

We applied three-dimensional (3D) analysis to optical coherence tomography angiography (OCTA) to measure macular ischemia in eyes affected by non-proliferative diabetic retinopathy (DR). A previously validated algorithm was applied to OCTA data in order to obtain 3D visualization of the retinal vasculature. Successively, a global thresholding algorithm was applied and two novel quantitative metrics were introduced: 3D vascular volume and 3D perfusion density. Two-dimensional (2D) OCTA metrics were also obtained with different binarization thresholds for comparison. Of the 30 patients included, 15 were diagnosed with DR and 15 were controls. The 3D vascular volume and 3D perfusion density were reduced in DR eyes (P < .0001). The 2D variables also significantly differ between groups. The 3D perfusion density had the highest area under the receiver operating characteristic curve (0.964) among tested variables. Assessing quantitative perfusion using 3D analysis is reliable and promising, and with an elevated diagnostic efficacy in identifying DR eyes.

Superior Survival Outcomes of a Polyethylene Glycol-20k Based Resuscitation Solution in a Preclinical Porcine Model of Lethal Hemorrhagic Shock.

To compare early outcomes and 24-hour survival after LVR with the novel polyethylene glycol-20k-based crystalloid (PEG-20k), WB, or hextend in a preclinical model of lethal HS. Posttraumatic HS is a major cause of preventable death. current resuscitation strategies focus on restoring oxygen-carrying capacity (OCC) and coagulation with blood products. Our lab shows that PEG-20k is an effective non-sanguineous, LVR solution in acute models of HS through mechanisms targeting cell swelling-induced microcirculatory failure. Male pigs underwent splenectomy followed by controlled hemorrhage until lactate reached 7.5-8.5 mmol/L. They were randomized to receive LVR with PEG-20k, WB, or Hextend. Surviving animals were recovered 4 hours post-LVR. Outcomes included 24-hour survival rates, mean arterial pressure, lactate, hemoglobin, and estimated intravascular volume changes. Twenty-four-hour survival rates were 100%, 16.7%, and 0% in the PEG-20k, WB, and Hextend groups, respectively (P= 0.001). PEG-20k significantly restored mean arterial press, intravascular volume, and capillary perfusion to baseline, compared to other groups. This caused complete lactate clearance despite decreased OCC. Neurological function was normal after next-day recovery in PEG-20k resuscitated pigs. Superior early and 24-hour outcomes were observed with PEG-20k LVR compared to WB and Hextend in a preclinical porcine model of lethal HS, despite decreased OCC from substantial volume-expansion. These findings demonstrate the importance of enhancing microcirculatory perfusion in early resuscitation strategies.

Prediction of early response to concurrent chemoradiotherapy in cervical cancer: Value of multi-parameter MRI combined with clinical prognostic factors

PurposeThis study aimed to investigate the prediction of early response to concurrent chemoradiotherapy (CCRT) through a combination of pretreatment multi-parametric magnetic resonance imaging (MRI) with clinical prognostic factors (CPF) in cervical cancer patients. MethodsEighty-five patients with pathologically confirmed cervical cancer underwent conventional MRI, intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI), and dynamic contrast-enhanced MRI (DCE-MRI) before CCRT. The patients were divided into non- and residual tumor groups according to post-treatment MRI. Univariable and multivariable analyses were performed to pretreatment MRI parameters and CPF between the two groups, and optimal thresholds and predictive performance for post-treatment residual tumor occurrence were estimated by drawing the receiver operating characteristic (ROC) curve. ResultsThere were 52 patients in non- and 33 in residual group. The residual group showed a lower perfusion fraction (f) value and volume transfer constant (Ktrans) value, a higher apparent diffusion coefficient (ADC) value, diffusion coefficient (D) value and volume fraction of extravascular extracellular space (Ve) value, and a higher stage than the non-residual tumor group (all P < .05). D, Ktrans, Ve and stage were independent prognostic factors. The combination of D, Ktrans and Ve improved the diagnostic performance compared with individual MRI parameters. A further combination of these three MRI parameters with stage exhibited the highest predictive performance. ConclusionsPretreatment D, Ktrans, Ve and stage were independent prognostic factors for cervical cancer. The predictive capacity of multi-parametric MRI was superior to individual MRI parameters. The combination of multi-parametric MRI with CPF further improved the predictive performance.

Hybrid Modelling of Transarterial Chemoembolisation Therapies (TACE) for Hepatocellular Carcinoma (HCC)

We extend an agent-based multiscale model of vascular tumour growth and angiogenesis to describe transarterial chemoembolisation (TACE) therapies. The model accounts for tumour and normal cells that are both nested in a vascular system that changes its structure according to tumour-related growth factors. Oxygen promotes nutrients to the tissue and determines cell proliferation or death rates. Within the extended model TACE is included as a two-step process: First, the purely mechanical influence of the embolisation therapy is modelled by a local occlusion of the tumour vasculature. There we distinguish between partial and complete responders, where parts of the vascular system are occluded for the first and the whole tumour vasculature is destroyed for the latter. In the second part of the model, drug eluding beads (DEBs) carrying the chemotherapeutic drug doxorubicin are located at destroyed vascular locations, releasing the drug over a certain time-window. Simulation results are parameterised to qualitatively reproduce clinical observations. Patients that undergo a TACE-treatment are categorised in partial and complete responders one day after the treatment. Another 90 days later reoccurance or complete response are detected by volume perfusion computer tomography (VPCT). Our simulations reveal that directly after a TACE- treatment an unstable tumour state can be observed, where regrowth and total tumour death have the same likeliness. It is argued that this short time-window is favorable for another therapeutical intervention with a less radical therapy. This procedure can shift the outcome to more effectiveness. Simulation results with an oxygen therapy within the unstable time-window demonstrate a potentially positive manipulated outcome. Finally, we conclude that our TACE model can motivate new therapeutical strategies and help clinicians analyse the intertwined relations and cross-links in tumours.

Novel delivery of cellular therapy to reduce ischemia reperfusion injury in kidney transplantation.

Ex vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimize organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC® ) possess potent immunomodulatory properties that could minimize ischemia reperfusion injury. We investigated the potential capability of MAPC cells in kidney NMP. Pairs (5) of human kidneys, from the same donor, were simultaneously perfused for 7 hours. Kidneys were randomly allocated to receive MAPC treatment or control. Serial samples of perfusate, urine, and tissue biopsies were taken for comparison. MAPC-treated kidneys demonstrated improved urine output (P=.009), decreased expression of injury biomarker NGAL (P=.012), improved microvascular perfusion on contrast-enhanced ultrasound (cortex P=.019, medulla P=.001), downregulation of interleukin (IL)-1β (P=.050), and upregulation of IL-10 (P<.047) and Indolamine-2, 3-dioxygenase (P=.050). A chemotaxis model demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (P<.001). Immunofluorescence revealed prelabeled MAPC cells in the perivascular space of kidneys during NMP. We report the first successful delivery of cellular therapy to a human kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to transplantation.

Parietal Perfusion Alterations in Parkinson's Disease Patients Without Dementia.

Fronto-parietal regions are involved in cognitive processes that are commonly affected in Parkinson's disease (PD). The aims of this study were to investigate cerebral blood flow (CBF) and gray matter (GM) volume within the regions belonging to the fronto-parietal circuit in people with PD (pwPD) without dementia, and to assess their association with cognitive performance. Twenty-seven pwPD without dementia (mean [SD] age = 67.4 [8.1] years, 20 males, mean [SD] Montreal Cognitive Assessment, MoCA score = 24.2 [2.9], median [IQR] Hoehn and Yahr scale = 1.5 [1–2]) and twenty-six age- and sex-matched healthy controls (HC) were scanned with arterial spin labeling (ASL) and T1-weighted magnetic resonance imaging (MRI) sequences to investigate CBF and GM volume, respectively. The cognitive performance of the enrolled pwPD was assessed with MoCA, Trail Making Test (TMT, part A, B, B-A), phonemic fluency and semantic fluency tests. The scores were adjusted for age and education. After standard preprocessing, CBF differences between pwPD and HC were tested with a voxel-wise approach. Voxel-based morphometry was used to compare pwPD and HC in terms of GM volume. Both voxel-wise comparisons between pwPD and HC were restricted to regions of the fronto-parietal circuit. The following additional voxel-wise analyses were performed within regions showing either perfusion or GM volume alterations: (1) correlation with neuropsychological test scores; (2) subgroup comparison after median split on each neuropsychological test score. Family-wise error-corrected (FWE) p-values lower than 0.05 were considered significant. Significant hypoperfusion was identified in the left inferior parietal lobule (IPL, ppeak = 0.037) and in the bilateral superior parietal lobule (SPL, left hemisphere: ppeak = 0.037; right hemisphere: ppeak = 0.049) of pwPD when compared to HC. No significant GM atrophy was observed. Local hypoperfusion did not correlate with any neuropsychological test scores. However, significantly lower CBF was observed in the left SPL and IPL of the pwPD subgroup who performed poorer on TMT part A in comparison with the pwPD subgroup that performed better. Perfusion alterations may occur in parietal regions of pwPD without dementia, and may be associated with lower visuomotor skills. Parietal CBF may be considered as a suitable early biomarker for longitudinal studies investigating cognitive decline in PD.

Quantifying Perfusion Properties with DCE-MRI Using a Dictionary Matching Approach

Perfusion properties can be estimated from pharmacokinetic models applied to DCE-MRI data using curve fitting algorithms; however, these suffer from drawbacks including the local minimum problem and substantial computational time. Here, a dictionary matching approach is proposed as an alternative. Curve fitting and dictionary matching were applied to simulated data using the dual-input single-compartment model with known perfusion property values and 5 in vivo DCE-MRI datasets. In simulation at SNR 60 dB, the dictionary estimate had a mean percent error of 0.4–1.0% for arterial fraction, 0.5–1.4% for distribution volume, and 0.0% for mean transit time. The curve fitting estimate had a mean percent error of 1.1–2.1% for arterial fraction, 0.5–1.3% for distribution volume, and 0.2–1.8% for mean transit time. In vivo, dictionary matching and curve fitting showed no statistically significant differences in any of the perfusion property measurements in any of the 10 ROIs between the methods. In vivo, the dictionary method performed over 140-fold faster than curve fitting, obtaining whole volume perfusion maps in just over 10 s. This study establishes the feasibility of using a dictionary matching approach as a new and faster way of estimating perfusion properties from pharmacokinetic models in DCE-MRI.

Opposed hemodynamic responses following increased excitation and parvalbumin-based inhibition

Understanding cellular contributions to hemodynamic activity is essential for interpreting blood-based brain mapping signals. Optogenetic studies examining cell-specific influences on local hemodynamics have reported that excitatory activity results in cerebral perfusion and blood volume increase, while inhibitory activity contributes to both vasodilation and vasoconstriction. How specific subpopulations of interneurons regulate the brain’s blood supply is less examined. Parvalbumin interneurons are the largest subpopulation of GABAergic neurons in the brain, critical for brain development, plasticity, and long-distance excitatory neurotransmission. Despite their essential role in brain function, the contribution of parvalbumin neurons to neurovascular coupling has been relatively unexamined. Using optical intrinsic signal imaging and laser speckle contrast imaging, we photostimulated awake and anesthetized transgenic mice expressing channelrhodopsin under a parvalbumin promoter. Increased parvalbumin activity reduced local oxygenation, cerebral blood volume, and cerebral blood flow. These “negative” hemodynamic responses were consistent within and across mice and reproducible across a broad range of photostimulus parameters. However, the sign and magnitude of the hemodynamic response resulting from increased parvalbumin activity depended on the type and level of anesthesia used. Opposed hemodynamic responses following increased excitation or parvalbumin-based inhibition suggest unique contributions from different cell populations to neurovascular coupling.

The utility of multiparametric MRI to characterize hypoxic tumor subvolumes in comparison to FMISO PET/CT. Consequences for diagnosis and chemoradiation treatment planning in head and neck cancer

Background and PurposeHypoxia is an essential metabolic marker that determines chemo- and radiation resistance in head-and-neck squamous cell carcinoma (HNSCC) patients. Our exploratory analysis aimed to identify multiparametric MRI (mpMRI) parameters linked to hypoxia that might be used as surrogate for [18F]FMISO-PET in diagnosis and chemoradiation treatment (CRT) of HNSCC. Materials and Methods21 patients undergoing definitive CRT for HNSCC were prospectively imaged with serial [18F]FMISO-PET and 3 Tesla mpMRI for T1- and T2-weighted and dynamic contrast-enhanced perfusion and diffusion-weighted measurements (ktrans, ve, kep, ADC) in weeks 0, 2 and 5 and FDG-PET in week 0. [18F]FMISO-PET-derived hypoxic subvolumes (HSV) and complementary non-hypoxic subvolumes (nonHSV) were created for tumor and lymph nodes and projected on the mpMRI scans after PET/MRI co-registration. MpMRI and [18F]FMISO-PET parameters within HSVs and nonHSVs were statistically compared. ResultsFMISO-PET-based HSVs of the primary tumors on MRI were characterized by lower ADC at all time points (p = 0.012 at baseline; p = 0.015 in week 2) and reduced interstitial space volume fraction ve and perfusion ktrans at baseline (p = 0.006, p = 0.047) compared to nonHSVs. Hypoxic lymph nodes were characterized by significantly lower ADC values at baseline (p = 0.039), but not at later time points and a reduction in ktrans-based perfusion at week 2 (p = 0.018). ConclusionMpMRI parameters differ significantly between hypoxic and non-hypoxic tumor regions, defined on FMISO-PET/CT as gold standard and might represent surrogate markers for tumor hypoxia. These findings suggest that mpMRI may be useful in the future as a surrogate modality for hypoxia imaging in order to personalize CRT.

Assessment of neovascularization in atherosclerotic carotid sinus plaques using quantitative contrast-enhanced ultrasound perfusion imaging

Aim. To assess the prospects of using quantitative contrast-enhanced ultrasound perfusion imaging of atherosclerotic carotid sinus plaques. Material and methods. The study included 5 men and 1 woman (59-76 years old, median 72) with symptomatic coronary sinus atherosclerosis. The inclusion criterion was history of ischemic stroke due to internal carotid artery lesion (NASCET &gt;60%). We performed contrast-enhanced ultrasound perfusion imaging of the carotid arteries, endarterectomy, studying pathomorphology of the removed plaque with the calculation of the neovascular density and the total number of neovessels with a diameter &lt;40 μm. Neovascularization was assessed by quantitative contrast-enhanced ultrasound 20 seconds after the 1 ml infusion of Sonovia (Bracco, Italy) and subsequent application of the flash. The analysis of dynamics of ultrasonic signal intensity in the atherosclerotic plaque was carried out by creating the curves of the ultrasonic signal intensity (dB)/time (s) over 3 segments of the cross section of the internal carotid artery long axis. The automatic calculation of the intensity dynamics took into account the parameter values in the studied areas within 20 s after the flash. The calculated coefficients (A, B, β) of the exponential equation for 3 atherosclerotic segments were recorded. Results. Perfusion and neovascularization were assessed in 27 segments of atherosclerotic plaques. The correlation relationships between the ultrasonic parameters of plaque perfusion and the severity of neovascularization were assessed according to the histological data. Significant correlations of the exponential curve coefficient β and histological parameters characterizing the prevalence of “young” vessels (&lt;40 microns) in the atherosclerotic plaque were revealed. Spearman’s R for the density of neovessels was 0,54; for the number of neovessels with a diameter &lt;40 μm. —0,66 (p&lt;0,01). Conclusion. Diagnosis of atherosclerotic plaque neovascularization becomes possible to quantify, assessing not only the presence of neovascular vessels, but also the perfusion intensity. The novel approach replaces the qualitative and semi-quantitative method for calculating the number of carotid plaques neovessels in vivo.

Efficacy of cystectasia in the treatment of ketamine-induced bladder contracture.

BackgroundThe treatment of ketamine-induced bladder contractures remains poorly studied. We therefore evaluated the efficacy of cystectasia with a sodium hyaluronate balanced solution in this kind of bladder contracture.MethodsEighteen patients presenting with ketamine-induced bladder contracture between July 2010 and February 2018 were selected and analysed. Ketamine was discontinued in all patients, who were then treated with weekly cystectasia (0.09% sodium hyaluronate balanced solution) 3 times. The volume of the first perfusion was twice the preoperatively measured bladder capacity, and the volume of the subsequent two perfusions was increased by 100 mL each time. The Pelvic Pain and Urgency/Frequency (PUF) symptom score, O’Leary-Sant Interstitial Cystitis (IC) Symptom Index (ICSI), IC Problem Index (ICPI), Quality of Life (QOL) score, and bladder capacity were recorded before surgery and 3 and 12 months after the 3rd expansion.ResultsNo significant complications were observed during the 3 expansions. Fourteen patients completed the full follow-up schedule. Preoperatively and at the 3- and 12-month follow-up evaluations performed after the 3rd expansion, the PUF symptom scores were 20.4±3.6, 11.5±3.1, and 13.2±3.3, respectively; the mean ICSI was 13.6±2.8, 7.7±2.3, and 8.2±2.5, respectively; the mean ICPI was 10.6±2.6, 7.3±2.1, and 7.7±2.5, respectively; and the mean QOL scores were 6.0±0, 2.1±0.5, and 2.7±0.8, respectively; and the mean bladder catheter volume was 83±27, 234±56, and 228±52 mL, respectively. There were significant differences between all preoperative and postoperative values.ConclusionsCystectasia with a sodium hyaluronate balanced solution is an effective treatment modality for ketamine-induced bladder contracture.

Encircling needling is superior to "Bangci"(focal center-side needling) in promoting wound healing in diabetic mice

To compare the therapeutic effects of "Bangci"(focal center-side needling) and encircling needling in promoting skin wound healing and local blood perfusion in diabetic mice. Thirty-two male C57BL/6N mice were randomized into normal, diabetic model, focal center-side needling and encircling needling groups (n=8 in each group). The skin wound model was prepared by cutting a piece of full-thickness skin at the mouse's back by using a puncher. One hour after modeling, two acupuncture needles were respectively inserted into the center of the wound and the spot at the normal skin about 0.5 cm away from the edge of the wound for mice of the focal center-side needling group, followed by EA (0.5 mA, 0.5 Hz) for 30 min. For mice of the encircling needling group, 4 acupuncture needles were respectively inserted into the upper, lower, left and right normal marginal skin around the wound, followed by EA stimulation with the same parameters as those of the center-side needling group. The wound conditions, diameter and area of the wound were monitored, and the wound blood perfusion volume was measured by using a laser speckle flowmeter. The wound shrinkage rates were significantly higher at the time-points of 3, 5, 7, 9 and 11 d after modeling in both focal center-side needling and encircling needling groups than in the model group (P<0.05), and on day 3, 5, 7 and 9 in the encircling needling group than in the focal center-side needling group (P<0.05). The wound healing time was obviously earlier in both focal center-side needling and encircling needling groups than in the model group (P<0.05), and in the encircling needling group than in the focal center-side needling group (P<0.05). Following modeling, the volume of wound blood perfusion was considerably higher from day 1 to 9 and markedly lower on day 11 in the model group than in the normal group (P<0.01), and after the intervention, the blood perfusion volume was considerably decreased on day 3, 5, 7 and 9 in both the focal center-side needling and encircling needling groups(P<0.05, P<0.01), and obviously increased on day 11 in the encircling needling group relevant to the model group (P<0.01).Comparison between post- and pre-EA stimulation showed that the immediate blood perfusion volume was significantly increased from day 1 to 11 after EA stimulation in both the focal center-side needling and encircling needling groups (P<0.01, P<0.05). The therapeutic effect of the encircling needling group was significantly superior to that of the focal center-side needling group in lowering blood perfusion volume from day 3 to 7, and in increasing blood perfusion volume on day 9 and 11 (P<0.01). Under the naked eyes, the conditions of exudation and inflammatory reaction, and the scar and granulation tissue were relatively milder and better respectively in both the center-side needling and encircling needling groups than in the model group. Both focal center-side needling and encircling needling can promote the skin wound healing by increasing the blood perfusion in diabetic mice, and the therapeutic effect of the encircling needling method was significantly superior to that of the focal center-side needling method.

Advanced imaging to assess longitudinal vascular changes in brain metastases treated with immune checkpoint inhibition.

2529 Background: Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) for melanoma and lung cancer. This breakthrough has prompted interest in evaluating ICI in BM of other histologies. However, accurately assessing intracranial response in patients undergoing ICI is a challenge, as current measures cannot distinguish pseudoprogression from true tumor progression. To shed light on potential biomarkers of response, we prospectively use perfusion MRI to identify characteristic vascular signatures in a BM-specific trial of ICI. Methods: As part of an ongoing phase II study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology, patients underwent advanced MRI that includes tumor volume measurements and perfusion imaging with dynamic susceptibility contrast MRI. To calculate volumetric radiographic response, all enhancing voxels were summated. A volumetric increase of &gt;40% was categorized as progressive disease (PD), a decrease of &gt;60% as partial response (PR), and stable disease (SD) as between -60% and +40%. Results: 53 patients have been enrolled, of whom 44 have received at least baseline advanced MR imaging. Histologies include 21 with breast cancer, 5 with non-small cell lung cancer, 4 with melanoma, and 13 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 33 evaluable patients include 4 PR, 10 SD, and 19 PD. On preliminary analysis, there was a correlation between increased tumor cerebral blood volume/flow with tumor progression. Correlation of additional vascular physiologic parameters (e.g. vessel caliber, tissue oxygenation) and volumetric response to patient outcome and standardized response criteria (iRANO) are ongoing. Conclusions: Pembrolizumab likely has anti-tumor efficacy in BM. Our data provides potential evidence that effective ICI is associated with a decrease in perfusion. Ongoing analyses to uncover additional vascular changes – specifically longitudinal metrics reflecting vascular structure and function - within BM to ICI are pending. These findings have potential to illustrate mechanisms of efficacy for ICI and biomarkers of response in this patient population.