Measurement Of Tissue Perfusion Research Articles

A multimodal tissue perfusion measurement approach for the evaluation of the effect of pimobendan, an inodilator, in a porcine sepsis model

Sepsis is associated with hypoperfusion and organ failure. The aims of the study were: 1) to assess the effect of pimobendan on macrocirculation and perfusion and 2) to describe a multimodal approach to the assessment of perfusion in sepsis and compare the evolution of the perfusion parameters.Eighteen anaesthetized female piglets were equipped for macrocirculation monitoring. Sepsis was induced by an infusion of Pseudomonas aeruginosa. After the occurrence of hypotension, animals were resuscitated. Nine pigs received pimobendan at the start of resuscitation maneuvers, the others received saline. Tissue perfusion was assessed using temperature gradients measured with infrared thermography (TG = core temperature – tarsus temperature), urethral perfusion index (uPI) derived from photoplethysmography and sublingual microcirculation (Sidestream dark field imaging device): De Backer score (DBs), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). Arterial lactate and ScvO2 were also measured.Pimobendan did not improve tissue perfusion nor macrocirculation. It did not allow a reduction in the amount of noradrenaline and fluids administered. Sepsis was associated with tissue perfusion disorders: there were a significant decrease in uPI, PPV and ScvO2 and a significant rise in TG. TG could significantly predict an increase in lactate. Resuscitation was associated with a significant increase in uPI, DBs, MFI, lactate and ScvO2. There were fair correlations between the different perfusion parameters.In this model, pimobendan did not show any benefit. The multimodal approach allowed the detection of tissue perfusion alteration but only temperature gradients predicted the increase in lactatemia.

Systemic acylcarnitine levels are affected in response to multiple injuries and hemorrhagic shock - an analysis of lipidomic changes in a standardized porcine model.

Along with recent advances in analytical technologies, TCA-cycle intermediates are increasingly identified as promising makers for cellular ischemia and mitochondrial dysfunction during hemorrhagic shock (HS). For traumatized patients, the knowledge of the role of lipid oxidation substrates is sparse. In this study, we aimed to analyze the dynamics of systemic acylcarnitine (AcCa) release in a standardized polytrauma model with HS. 52 male pigs (50 ± 5 kg) were randomized into two groups: Group IF (isolated fracture) was subject to a standardized femur shaft fracture. Group PT (polytrauma) was subject to a femur fracture, followed by blunt chest trauma, liver laceration and a pressure controlled hemorrhagic shock for 60 min. Resuscitation was performed with crystalloids. Fractures were stabilized by intramedullary nailing. Venous samples were collected at 6 timepoints (baseline, trauma, resuscitation, 2 h, 4 h and 6 h). Lipidomic analysis was performed via liquid chromatography coupled mass spectrometry. Measurements were collated with clinical markers and near-infrared spectrometry measurements (NIRS) of tissue perfusion. Longitudinal analyses were performed with linear mixed models and spearman's correlations were calculated. A p-value of 0.05 was defined as threshold for statistical significance. From a total of 303 distinct lipids, we identified two species of long-chain AcCas. Both showed a highly significant (p < 0.001) two-fold increase after HS in Group PT that promptly normalized after resuscitation. This increase was associated with a significant decrease of the base excess (p = 0.005) but recovery after resuscitation was faster. For both AcCas, there were significant correlations with decreased muscle tissue oxygen delivery (p = 0.008, p = 0.003) and significant time-lagged correlations with the increase of creatine kinase (p < 0.001, p < 0.001). Our results point to plasma AcCas as a possible indicator for mitochondrial dysfunction and cellular ischemia in HS. The more rapid normalization after resuscitation in comparison to acid base changes may warrant further investigation. Experimental Animal Model. N/A.

Effects of endoluminal vacuum sponge therapy on the perfusion of gastric conduit in a porcine model for esophagectomy.

After esophagectomy, the postoperative rate of anastomotic leakage is up to 30% and is the main driver of postoperative morbidity. Contemporary management includes endoluminal vacuum sponge therapy (EndoVAC) with good success rates. Vacuum therapy improves tissue perfusion in superficial wounds, but this has not been shown for gastric conduits. This study aimed to assess gastric conduit perfusion with EndoVAC in a porcine model for esophagectomy. A porcine model (n = 18) was used with gastric conduit formation and induction of ischemia at the cranial end of the gastric conduit with measurement of tissue perfusion over time. In three experimental groups EndoVAC therapy was then used in the gastric conduit (- 40, - 125, and - 200 mmHg). Changes in tissue perfusion and tissue edema were assessed using hyperspectral imaging. The study was approved by local authorities (Project License G-333/19, G-67/22). Induction of ischemia led to significant reduction of tissue oxygenation from 65.1 ± 2.5% to 44.7 ± 5.5% (p < 0.01). After EndoVAC therapy with - 125 mmHg a significant increase in tissue oxygenation to 61.9 ± 5.5% was seen after 60 min and stayed stable after 120 min (62.9 ± 9.4%, p < 0.01 vs tissue ischemia). A similar improvement was seen with EndoVAC therapy at - 200 mmHg. A nonsignificant increase in oxygenation levels was also seen after therapy with - 40 mmHg, from 46.3 ± 3.4% to 52.5 ± 4.3% and 53.9 ± 8.1% after 60 and 120 min respectively (p > 0.05). An increase in tissue edema was observed after 60 and 120 min of EndoVAC therapy with - 200 mmHg but not with - 40 and - 125 mmHg. EndoVAC therapy with a pressure of - 125 mmHg significantly increased tissue perfusion of ischemic gastric conduit. With better understanding of underlying physiology the optimal use of EndoVAC therapy can be determined including a possible preemptive use for gastric conduits with impaired arterial perfusion or venous congestion.

Switchable LED-based laparoscopic multispectral system for rapid high-resolution perfusion imaging.

Multispectral imaging (MSI) is an approach for real-time, quantitative, and non-invasive tissue perfusion measurements. Current laparoscopic systems based on mosaic sensors or filter wheels lack high spatial resolution or acceptable frame rates. To develop a laparoscopic system for MSI-based color video and tissue perfusion imaging during gastrointestinal surgery without compromising spatial or temporal resolution. The system was built with 14 switchable light-emitting diodes in the visible and near-infrared spectral range, a 4K image sensor, and a 10mm laparoscope. Illumination patterns were created for tissue oxygenation and hemoglobin content monitoring. The system was calibrated to a clinically approved laparoscopic hyperspectral system using linear regression models and evaluated in an occlusion study with 36 volunteers. The root mean squared errors between the MSI and reference system were 0.073 for hemoglobin content, 0.039 for oxygenation in deeper tissue layers, and 0.093 for superficial oxygenation. The spatial resolution at a working distance of 45mm was . The effective frame rate was 20fps. High-resolution perfusion monitoring was successfully achieved. Hardware optimizations will increase the frame rate. Parameter optimizations through alternative illumination patterns, regression, or assumed tissue models are planned. Intraoperative measurements must confirm the suitability during surgery.

Intravoxel incoherent motion (IVIM) detects femoral head ischemia in a piglet model of Legg-Calvé-Perthes disease.

There is a clinical need for alternatives to gadolinium contrast-enhanced magnetic resonance imaging (MRI) to facilitate early detection and assessment of femoral head ischemia in pediatric patients with Legg-Calvé-Perthes disease (LCPD), a juvenile form of idiopathic osteonecrosis of the femoral head. The purpose of this study was to determine if intravoxel incoherent motion (IVIM), a noncontrast-enhanced MRI method to simultaneously measure tissue perfusion and diffusion, can detect femoral head ischemia using a piglet model of LCPD. Twelve 6-week-old piglets underwent unilateral hip surgery to induce complete femoral head ischemia. The unoperated, contralateral femoral head served as a perfused control. The bilateral hips of the piglets were imaged in vivo at 3T MRI using IVIM and contrast-enhanced MRI 1 week after surgery. Median apparent diffusion coefficient (ADC) and IVIM parameters (diffusion coefficient: Ds; perfusion coefficient: Df; perfusion fraction: f; and perfusion flux: f*Df) were compared between regions of interest comprising the epiphyseal bone marrow of the ischemic and control femoral heads. Contrast-enhanced MRI confirmed complete femoral head ischemia in 11/12 piglets. IVIM perfusion fraction (f) and flux (f*Df) were significantly decreased in the ischemic versus control femoral heads: on average, f decreased 47 ± 27% (Δf = -0.055 ± 0.034; p = 0.0003) and f*Df decreased 50 ± 27% (Δf*Df = -0.59 ± 0.49 × 10-3 mm2/s; p = 0.0026). In contrast, IVIM diffusion coefficient (Ds) and ADC were significantly increased in the ischemic versus control femoral heads: on average, Ds increased 78 ± 21% (ΔDs = 0.60 ± 0.14 × 10-3 mm2/s; p < 0.0001) and ADC increased 60 ± 36% (ΔADC = 0.50 ± 0.23 × 10-3 mm2/s; p < 0.0001). In conclusion, IVIM is sensitive in detecting bone marrow ischemia in a piglet model of LCPD.

Near-Infrared Spectroscopy for Continuous Noninvasive Monitoring of Free Flap in Head and Neck Reconstruction: Systematic Review of the Literature and Personal Experience.

Buried free flaps represent a reconstructive challenge concerning monitoring of vitality, which is fundamental for an early detection of flap failure and prompt surgical salvage. Many flap monitoring techniques have been developed over time, and there is still no consensus concerning the best monitoring technique for buried reconstructions. We performed a systematic review of the literature on NIRS monitoring for head and neck free flaps. Moreover, we presented a case of orbital reconstruction through a buried free myo-fascial anterolateral tight flap (ALTF) in which postoperative monitoring was performed by means of NIRS. Four studies were included with a total of 200 monitored head and neck free flap reconstructions. Flap survival was reported in 96.5% of studies (n = 193/200) with a 3.5% of total flap failure rate (n = 7/200). We monitored the buried myo-fascial ALTF for 7 post-operative days measuring a regional oxygen saturation (rSO2) ranging from 55% to 72% (mean = 66%). This device appeared to be an efficient choice for monitoring buried flaps, thanks to its ability to measure tissue perfusion deep under the skin, to the continuous availability of recorded data on the monitor, and to its low impact on the patient. Further prospective studies are advised in order to standardize this monitoring technique and define warning values.

Intra-abdominal laparoscopic assessment of organs perfusion using imaging photoplethysmography.

An objective evaluation of the functional state and viability of biological tissues during minimally invasive surgery remains unsolved task. Various non-contact methods for evaluating perfusion during laparoscopic surgery are discussed in the literature, but so far there have been no reports of their use in clinical settings. Imaging photoplethysmography (iPPG) is a new method for quantitative assessment of perfusion distribution along the tissue. This is the first study in which we demonstrate successful use of iPPG to assess perfusion of organs during laparoscopic surgery in an operation theater. We used a standard rigid laparoscope connected to a standard digital monochrome camera, and abdominal organs were illuminated by green light. A distinctive feature is the synchronous recording of video frames and electrocardiogram with subsequent correlation data processing. During the laparoscopically assisted surgeries in nine cancer patients, the gradient of perfusion of the affected organs was evaluated. In particular, measurements were carried out before preparing a part of the intestine or stomach for resection, after anastomosis, or during physiological tests. The spatial distribution of perfusion and its changes over time were successfully measured in all surgical cases. In particular, perfusion gradient of an intestine before resection was visualized and quantified by our iPPG laparoscope in all respective cases. It was also demonstrated that systemic administration of norepinephrine leads to a sharper gradient between well and poorly perfused areas of the colon. In four surgical cases, we have shown capability of the laparoscopic iPPG system for intra-abdominal assessment of perfusion in the anastomosed organs. Moreover, good repeatability of continuous long-term measurements of tissue perfusion inside the abdominal cavity was experimentally demonstrated. Our study carried out in real clinical settings has shown that iPPG laparoscope is feasible for intra-abdominal visualization and quantitative assessment of perfusion distribution.

Doppler ultrasonographic evaluation of tissue revascularization following connective tissue graft at implant sites.

To assess the Doppler ultrasonographic tissue perfusion at dental implant sites augmented with connective tissue graft (CTG) using coronally advanced flap (CAF) or tunnel technique (TUN). Twenty-eight patients presenting with isolated healthy peri-implant soft-tissue dehiscence (PSTD) were included in this randomized clinical trial. PSTDs were treated with either CAF + CTG or TUN + CTG. Ultrasound scans were taken at baseline, 1 week, 1 month, 6 months and 12 months. Tissue perfusion at the mid-facial, mesial and distal aspects of the implant sites was assessed by colour Doppler velocity (CDV) and power Doppler imaging (PDI). Early vascularization of the graft and the flap at 1 week and at 1 month were evaluated via dynamic tissue perfusion measurements (DTPMs), includingflow intensity (FI), mean perfusion relief intensity (pRI) and mean perfused area (pA). Regression analysis did not reveal significant differences in terms of mid-facial CDV and PDI changes between CAF and TUN over 12 months (p > .05), while significant differences between the two groups were observed at the interproximal areas (p < .001 for both CDV and PDI changes). Higher early DTPMs were observed at the TUN-treated sites in terms of mean FI of the graft (p = .027) and mean FI (p = .024) and pRI of the flap (p = .031) compared with CAF-treated sites at 1 week. Assessment of the FI direction showed that CTG perfusion at 1 week and at 1 month mainly occurred from the flap towards the implant/bone. Early tissue perfusion outcomes were found to be associated with the 12-month mean PSTD coverage and mucosal thickness gain. Doppler ultrasonography shows tissue perfusion changes occurring at implant sites augmented with CTG. The main differences in tissue perfusion between CAF and TUN were observed at the interproximal sites, with early perfusion associated with clinical and volumetric outcomes at 12 months.

Eficacia y seguridad de un compuesto de ácidos grasos hiperoxigenados en la mejora de la microcirculación de la púrpura fulminante en pacientes pediátricos con sepsis: estudio piloto

IntroductionPurpura fulminans (PF) is a serious complication of sepsis resulting from a set of alterations characterised by the development of ecchymotic haemorrhagic lesions and skin necrosis. AimTo analyse the efficacy and safety of the topical application of HOFA compound, in the cutaneous microcirculation of PF lesions in paediatric patients affected by sepsis. Material and methodsA prospective quasi-experimental pre-test/post-test single-group conducted in a Paediatric Intensive Care Unit of a third level hospital was performed. Paediatric patients aged 0-18 years with sepsis were included. Somatic oximetry values were measured before and after application of HOFAs every 4hours over the first three days of the patients’ hospitalisation. Patient's socio-demographic and clinical variables and somatic oximetry by placing a sensor for measuring tissue perfusion on the area with PF were determined. ResultsFour patients were recruited, with a median age of 98 months. The purpuric lesions measured were mainly located on both feet and hands and, in two patients, also on the lateral malleoli and calves of both lower extremities. A total of 225 measurements were obtained, with mean pre-intervention scores of 71.17±15.65% versus 73.68±14.83% post-intervention. Statistical significance (p<0.001) was observed upon comparison of the pre- and post-intervention measurements. ConclusionsEarly and continued application of HOFAs in the management of sepsis-induced PF is an effective and safe practice in the cases analysed. In more than half of the episodes analysed, an increase in tissue microcirculation was observed after the application of HOFAs, with no adverse events.

Efficacy and safety of a hyperoxygenated fatty acid compound in improving the microcirculation of purpura fulminans in paediatric patients with sepsis: a pilot study

IntroductionPurpura fulminans (PF) is a serious complication of sepsis resulting from a set of alterations characterised by the development of ecchymotic haemorrhagic lesions and skin necrosis. AimTo analyse the efficacy and safety of the topical application of HOFA compound, in the cutaneous microcirculation of PF lesions in paediatric patients affected by sepsis. Material and methodsA prospective quasi-experimental pre-test/post-test single-group conducted in a Paediatric Intensive Care Unit of a third level hospital was performed. Paediatric patients aged 0–18 years with sepsis were included. Somatic oximetry values were measured before and after application of HOFAs every 4h over the first three days of the patients’ hospitalisation. Patient’s socio-demographic and clinical variables and somatic oximetry by placing a sensor for measuring tissue perfusion on the area with PF were determined. ResultsFour patients were recruited, with a median age of 98 months. The purpuric lesions measured were mainly located on both feet and hands and, in two patients, also on the lateral malleoli and calves of both lower extremities. A total of 225 measurements were obtained, with mean pre-intervention scores of 71.17±15.65% versus 73.68±14.83% post-intervention. Statistical significance (p<0.001) was observed upon comparison of the pre- and post-intervention measurements. ConclusionsEarly and continued application of HOFAs in the management of sepsis-induced PF is an effective and safe practice in the cases analysed. In more than half of the episodes analysed, an increase in tissue microcirculation was observed after the application of HOFAs, with no adverse events.

The Utility of Contrast Enhanced Ultrasound and Elastography in the Early Detection of Fibro-Stenotic Ileal Strictures in Children with Crohn's Disease.

Crohn's disease (CD) is a chronic, idiopathic bowel disorder that can progress to partial or complete bowel obstruction. At present, there are no reliable diagnostic tests that can readily distinguish between acute inflammatory, purely fibrotic and mixed inflammatory and fibrotic. Our aim is to study the utility of contrast enhanced ultrasound (CEUS) in combination with shear wave elastography (SWE) to differentiate fibrotic from inflammatory strictures in children with obstructive CD of the terminal ileum. Twenty-five (19 male) children between 2016-2021 with CD of the terminal ileum were recruited into the study. Among these patients, 22 had CEUS kinetic measurements of tissue perfusion, including wash-in slope (dB/sec), peak intensity (dB), time to peak intensity (sec), area under the curve (AUC) (dB sec), and SWE. In total, 11 patients required surgery due to bowel obstruction. Histopathologic analysis was performed by a pathologist who was blinded to the CEUS and SWE test results. Patients that underwent surgical resection had significantly higher mean area under the curve on CEUS compared to patients responsive to medical therapy (p=0.03). The AUC also correlated with the degree of hypertrophy and the percent fibrosis of the muscularis propria, as determined by histopathologic grading (p<0.01). There was no difference in the mean elastography measurements between these two patient groups. CEUS is a useful radiological technique that can help identify pediatric patients with medically refractory obstructive fibrotic strictures of the terminal ileum that should be considered for early surgical resection.

Comparison of laser speckle contrast imaging with laser Doppler perfusion imaging for tissue perfusion measurement.

Laser-based tissue perfusion monitoring techniques have been increasingly used in animal and human research to assess blood flow. However, these techniques use arbitrary units, and knowledge about their comparability is scarce. This study aimed to model the relationship between laser speckle contrast imaging (LSCI) and laser Doppler perfusion imaging (LDPI), for measuring tissue perfusion over a wide range of blood flux values. Fifteen healthy volunteers (53% female, median age 29 [IQR 22-40] years) were enrolled in this study. We performed iontophoresis with sodium nitroprusside on the forearm to induce regional vasodilation to increase skin blood flux. Besides, a stepwise vascular occlusion was applied on the contralateral upper arm to reduce blood flux. Both techniques were compared using a linear mixed model analysis. Baseline blood flux values measured by LSCI were 33 ± 6.5 arbitrary unit (AU) (Coefficient of variation [CV]=20%) and by LDPI 60 ± 11.5AU (CV=19%). At the end of the iontophoresis protocol, the regional blood flux increased to 724 ± 412% and 259 ± 87% of baseline measured by LDPI and LSCI, respectively. On the other hand, during the stepwise vascular occlusion test, the blood flux reduced to 212 ± 40% and 412 ± 177% of its baseline at LDPI and LSCI, respectively. A strong correlation was found between the LSCI and LDPI instruments at increased blood flux with respect to baseline skin blood flux; however, the correlation was weak at reduced blood flux with respect to baseline. LSCI and LDPI instruments are highly linear for blood flux higher than baseline skin blood flux; however, the correlation decreased for blood flux lower than baseline. This study's findings could be a basis for using LSCI in specific patient populations, such as burn care.

Assessment of the microvascular perfusion using sidestream dark‐field imaging in healthy newborn foals

Different methods to measure tissue perfusion are available in equine neonatology, but they are not representative of microvascular derangements. To evaluate the feasibility of the sidestream dark-field (SDF) capillaroscopy to visualize the capillary microvasculature in conscious newborn foals, the differences between two imaging sites and times of measurements, and the measurements' reproducibility. Seventeen healthy newborn foals were enrolled. Three sites at the upper and lower lip mucosa were assessed by SDF, using a hand-held capiscope, at 24 h and at 4-5 days after birth. Videos were assessed independently by two observers for quality and for semiquantitative calculation of microvascular parameters, including vascular density (VD), microvascular flow index (MFI), proportion of perfused vessels (PPV), and functional capillary density (FCD). Data were analyzed using unpaired and paired Student's T-tests to assess differences between sites and time-points. Bland-Altman plots and intraclass correlation coefficient (ICC) were used to assess measurement reproducibility. Differences were found between the upper and the lower lip for VD at both 24 h and 4-5 days, and for FCD at 24 h, and between the two time-points for PPV at the lower lip. ICC for measurement reproducibility was good for all parameters (0.64-0.79) for the lower lip, and was good for VD and FCD (0,76-0,79) and fair to moderate for MFI and PPV (0.31-0.41) for the upper lip. Measurement of the capillary microvasculature is feasible in the conscious newborn foal. The lower lip has the best measurement reproducibility. Further investigations are warranted in cardiovascularly compromised cases, particularly in septic foals.

Computed Tomography Angiography Compared with Computed Tomography Perfusion in the Diagnosis of Cerebral Vasospasm: A Systematic Review and Meta-Analysis

Cerebral vasospasm (CV) is a serious complication after subarachnoid hemorrhage; however, swift identification can be challenging. Computed tomography perfusion (CTP) directly measures tissue perfusion and may better screen for CV compared with other modalities. This systematic review summarizes studies assessing the diagnostic performance of computed tomography angiography (CTA) and CTP in identifying CV. The search strategy drew from English language publications in the PubMed, Embase, Medline, and Cochrane databases from January 1996 to September 2021. Diagnosis of CV by digital subtraction angiography was the reference standard. Pooled sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), positive likelihood ratios, negative likelihood ratios, and summary receiver operating characteristic curve were calculated. The methodological index for nonrandomized studies tool was employed to assess the quality of the studies. The search generated 22 studies. Seven CTA studies and 6 CTP investigations provided sufficient data for meta-analysis. Following pooled estimates, CTA carried a sensitivity of 0.76 (95% confidence interval [CI], 0.72-0.80), specificity of 0.93 (95% CI, 0.92-0.95), PPV of 0.77 (95%,0.76-0.79), and NPV of 0.81 (95%, 0.79-0.82). CTP carried a sensitivity of 0.86 (95%, 0.81-0.92), specificity of 0.97 (95%, 0.95-0.98), PPV of 0.94 (0.89-0.98), and NPV of 0.94 (0.91-0.97). Using the methodological index for nonrandomized studies tool, the evidence was rated as overall moderate quality. This meta-analysis on the diagnostic performance of CTA and CTP in identifying CV suggests that CTP may carry greater diagnostic accuracy compared with CTA. The clinical significance of this difference should be delineated through future prospective studies.

Mapping glycine uptake and its metabolic conversion to glutathione in mouse mammary tumors using functional mass spectrometry imaging.

Although glutathione plays a key role in cancer cell viability and therapy response there is no clear trend in relating the level of this antioxidant to clinical stage, histological grade, or therapy response in patient tumors. The likely reason is that static levels of glutathione are not a good indicator of how a tissue deals with oxidative stress. A better indicator is the functional capacity of the tissue to maintain glutathione levels in response to this stress. However, there are few methods to assess glutathione metabolic function in tissue. We have developed a novel functional mass spectrometry imaging (fMSI) method that can map the variations in the conversion of glycine to glutathione metabolic activity across tumor tissue sections by tracking the fate of three glycine isotopologues administered in a timed sequence to tumor-bearing anesthetized mice. This fMSI method generates multiple time point kinetic data for substrate uptake and glutathione production from each spatial location in the tissue. As expected, the fMSI data shows glutathione metabolic activity varies across the murine 4T1 mammary tumor. Although glutathione levels are highest at the tumor periphery there are regions of high content but low metabolic activity. The timed infusion method also detects variations in delivery of the glycine isotopologues thereby providing a measure of tissue perfusion, including evidence of intermittent perfusion, that contributes to the observed differences in metabolic activity. We believe this new approach will be an asset to linking molecular content to tissue function.

Using micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) for trace metal imaging in the development of MRI contrast agents for prostate cancer imaging

BackgroundContrast agents (CA) are administered in magnetic resonance imaging (MRI) clinical exams to measure tissue perfusion, enhance image contrast between adjacent tissues, or provide additional biochemical information in molecular MRI. The efficacy of a CA is determined by the tissue distribution of the agent and its concentration in the extracellular space of all tissues. MethodsIn this work, micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) was used to examine and characterize a gadolinium-based zinc-sensitive agent (GdL2) currently under development for detection of prostate cancer (PCa) by MRI. Prostate tissue samples were collected from control mice and mice with known PCa after an MRI exam that included injection of GdL2. The samples were raster scanned to investigate trends in Zn, Gd, Cu, Fe, S, P, and Ca. ResultsSignificant Zn and Gd co-localization was observed in both healthy and malignant tissues. In addition, a marked decrease in Zn was found in the lateral lobe of the prostate obtained from mice with PCa. ConclusionWe demonstrate here that µ-SRXRF is a useful tool for monitoring the distribution of several elements including Zn and Gd in animal models of cancer. The optimized procedures for tissue preparation, processing, data collection, and analysis are described.

Abstract 303: Monitoring Tissue Oxygen Dynamics With A Novel Implantable Hydrogel Sensor In Patients With Pad

Objective: Tissue perfusion measurement remains a fundamental challenge in management of peripheral arterial disease (PAD) patients. Better measurement of baseline and dynamic changes after revascularization would aid clinical judgement. The Wireless Lumee® Oxygen System represents a novel approach to tracking tissue oxygen via a subcutaneous hydrogel that provides noninvasive optical oxygen measurements. This study’s objective was to assess the correlation of the Lumee sensor with transcutaneous oximetry (tcpO2) in PAD patients. Methods: The Lumee® Oxygen System is a subcutaneously placed hydrogel (0.5x0.5x5mm). Optical signals are captured with a skin surface reader sensing extravascular oxygenation. A pilot study assessed in vivo performance with inclusion criteria of peripheral arterial disease (Rutherford I-IV). Sensors were injected in the arm and foot and oxygenation measured before, during, and after proximal blood pressure cuff inflation (Figure) and Buerger’s Test modulation. The correlation (R) of oxygenation between tcpO2 and Lumee® was assessed following sensor placement at 2, 10, 90, 180, and 365 days. Results: Eleven subjects had 148 occlusion modulations over 199 days. Mean age was 67 years (range: 55-88), with 9% females, 45% White and 55% Black Race, Rutherford class I: 36%, II: 36%, III:27%. The median ABI was 0.83 (IQR0.69-1.14). In the arm, modulation was 56.9±24.6% (Lumee) and 84.7±9.2% (tcpO2), R:0.81. In the foot, modulation was 63.4±22.7% (Lumee) and 80.4±15.5% (tcpO2), R:0.79. No injection related adverse events occurred. Conclusion: Occlusion related changes in tissue oxygen can be detected by both tcpO2 and the Lumee sensor which strongly correlate in both the arm and foot. This pilot phase study supports expansion of the trial. The Lumee sensor shows promise for future evaluation of tissue oxygenation in PAD patients, which could be used to assess changes in tissue oxygenation over time and following revascularization.

Recovery of organ-specific tissue oxygen delivery at restrictive transfusion thresholds after fluid treatment in ovine haemorrhagic shock

BackgroundFluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient’s own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock.MethodsA model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30–40 mmHg) and oxygen debt (lactate > 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA.ResultsEach treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (p > 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (p < 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels (p < 0.0001). The novel crystalloid supported rapid peripheral vasodilation (p = 0.014) and tended to achieve tissue oxygen delivery targets earlier. PRBC supported earlier renal oxygen delivery (p = 0.012) but delayed peripheral perfusion (p = 0.034).ConclusionsCrystalloids supported vital organ oxygen delivery after massive haemorrhage, despite haemodilution to < 70 g/L, confirming that restrictive transfusion thresholds are appropriate to support oxygen delivery. Non-invasive tissue perfusion and oximetry technologies merit further clinical appraisal to guide treatment for massive haemorrhage in the context of Patient Blood Management.

Role of Magnetic Resonance Perfusion Imaging in Acute Stroke: Arterial Spin Labeling Versus Dynamic Susceptibility Contrast-Enhanced Perfusion.

Introduction: The role of perfusion neuroimaging in managing cases of acute ischemic stroke (AIS) is to identify ischemic penumbra and regions of hypo-perfusion, which can be salvaged. Dynamic susceptibility contrast (DSC) perfusion imaging techniques have been the main magnetic resonance imaging (MRI) perfusion techniques used to identify AIS. Arterial spin labelling (ASL) is an alternative non-invasive perfusion technique, which permits tissue perfusion measurement without any need for administration of exogenous contrast agents. The objective was to compare the diagnostic accuracy of ASL perfusion MRI versus DSC enhanced perfusion MRI in detecting perfusion-diffusion mismatch of varying volumes in acute ischemic stroke.Materials and methods: A hospital-based observational cross-sectional study was done in a tertiary care institute in Tamil Nadu between December 2018 to October 2019. Fifty-five subjects aged more than 18 years referred to the Radio-diagnosis department (less than 24 hours since the onset of weakness) for emergency assessment of suspected acute stroke were subjected to MRI stroke scan protocol. Then AIS cases were evaluated with ASL and DSC perfusion-weighted imaging. The collected data was entered in Excel (Microsoft, Redmond, WA, USA). IBM SPSS version 22 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. Receiver operating characteristic (ROC) analysis was done to assess the predictive validity of ASL in predicting DSC mismatch. The diagnostic accuracy of ASL was the primary outcome variable. P-value < 0.05 was considered statistically significant.Results: Forty-four subjects confirmed as stroke were included in the final analysis. Their mean (±SD) age was 53.84 (±10.80) years. 72.7% were males. The majority (53.8%) presented during the acute stage of cerebral infarction (53.8%). The majority (45.5%) had hemiplegia followed by aphasia (27.3%). The major vascular territory involved was the middle cerebral artery (54.5%). The sensitivity, specificity, positive predictive value, and negative predictive value of ASL (non-contrast) in predicting DSC (contrast) mismatch was found to be 71.43%, 78.57%, 83.33%, and 64.71% respectively.Conclusion: ASL MR has the potential to replace MRI DSC perfusion in the future imaging diagnostic work-up for stroke. However, further studies are required to validate its role as the first-line imaging for stroke therapy.

Detecting Changes in Tissue Perfusion With Hyperspectral Imaging and Thermal Imaging Following Endovascular Treatment for Peripheral Arterial Disease

Purpose Hyperspectral imaging (HSI) and thermal imaging allow contact-free tissue perfusion measurements and may help determine the effect of endovascular treatment (EVT) in patients with peripheral arterial disease. This study aimed to detect changes in perfusion with HSI and thermal imaging peri-procedurally and determine whether these changes can identify limbs that show clinical improvement after 6 weeks. Methods Patients with Rutherford class 2–6 scheduled for EVT were included prospectively. Hyperspectral imaging and thermal imaging were performed directly before and after EVT. Images were taken from the lateral side of the calves and plantar side of the feet. Concentrations of (de)oxyhemoglobin, oxygen saturation, and skin temperature were recorded. Angiographic results were determined on completion angiogram. Clinical improvement 6 weeks after EVT was defined as a decrease ≥ one Rutherford class. Peri-procedural changes in perfusion parameters were compared between limbs with and without good angiographic results or clinical improvement. To identify limbs with clinical improvement, receiver operating characteristic (ROC) curves were used to determine cutoff values for change in HSI. Results Included were 23 patients with 29 treated limbs. Change in HSI values and temperature was not significantly different between limbs with good and poor angiographic results. Change in peri-procedural deoxyhemoglobin, determined by HSI, at the calves and feet was significantly different between limbs with and without clinical improvement at 6 week follow-up (p=0.027 and p=0.017, respectively). The ROC curve for change in deoxyhemoglobin at the calves showed a cutoff value of ≤1.0, and ≤−0.5 at the feet, which were discriminative for clinical improvement (sensitivity 77%; specificity 75% and sensitivity 62%; specificity 88%, respectively). Conclusions HSI can detect changes in perfusion at the calves after EVT in patients with Rutherford class 2–6. Peri-procedural deoxyhemoglobin changes at the calves and feet are significantly different between limbs with and without clinical improvement. Decrease in deoxyhemoglobin directly after EVT may identify limbs that show clinical improvement 6 weeks after EVT.