Perfusion Response Research Articles

Neurovascular toxicity of N-methyl-d-aspartate is markedly enhanced in the developing mouse central nervous system.

Penumbral perfusion is critical to brain viability. Proximal arterial occlusion and deep brain stroke has variable effect on cortical dysfunction. Cortical microvessel collaterals may be recruited and at times sufficient for partial parenchymal perfusion. Postnatal neural and endothelial cells are markedly vulnerable to glutamate excitotoxicity. Early vascular cell stress may promote partial protective neural preconditioning though postnatally a developmental window of the cerebral microvasculature may be particularly vulnerable to injury. We tested the hypothesis that postnatal NMDA excitotoxic injury, when cerebral endothelial cells' central energy source is via glycolysis, is age specific. Neurovascular responses of cortical viability were directly identified with diffuse reflectance patterns of perfusion properties in a non-invasive manner, over time. Histological evaluation for neural and vascular cytoarchitectonic abnormalities were evaluated 4- 7days post injury. Optical diffuse reflectance recordings were obtained at the injection site prior to, immediately after and 48h post injury. Extent of neurovascular injury at the infarct zone was greatest at PND 5 and cortical perfusion responses identified with recordings of pattern change. These data further suggest excitotoxic injury to both neural and vascular cells, in vivo, can enhance CNS injury in the young and neuroprotective strategies may benefit from vascular directed therapies.

Value of functional magnetic resonance imaging in predicting outcomes of neoadjuvant chemoradiotherapy in rectal cancer

Rectal cancer is one of the common cancers which poses a threat to the health of mankind. In recent years. Multi-modality treatment strategies for locally advanced rectal cancer improve the treatment efficiency. Accurate prediction of the treatment response after the neoadjuvant chemoradiotherapy (CRT) can guide more suitable treatment strategy. MERCURY study proved the prognostic value of post-CRT standard morphologic MRI(T2-weighted) assessment of tumor regression grade(TRG), and MRI assessment of circumferential resection margin can guide the definitive surgery. Compared with standard morphologic MRI (T2-weighted), functional MRI, including diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE) MRI, has shown more promising results for the prediction of therapeutic response in rectal cancer. The addition of diffusion-weighted images to T2-weighted images improves the accuracy of restaging examinations for determination of complete pathologic responders. DCE can reflect the tumor micro-vascular environment, and the change of perfusion in response to treatment. These images have the potential to improve the accuracy of therapeutic response in rectal cancer.

Cerebral oxygenation and regional cerebral perfusion responses with resistance breathing during central hypovolemia.

Resistance breathing improves tolerance to central hypovolemia induced by lower body negative pressure (LBNP), but this is not related to protection of anterior cerebral blood flow [indexed by mean middle cerebral artery velocity (MCAv)]. We hypothesized that inspiratory resistance breathing improves tolerance to central hypovolemia by maintaining cerebral oxygenation (ScO2), and protecting cerebral blood flow in the posterior cerebral circulation [indexed by posterior cerebral artery velocity (PCAv)]. Eight subjects (4 male/4 female) completed two experimental sessions of a presyncopal-limited LBNP protocol (3 mmHg/min onset rate) with and without (Control) resistance breathing via an impedance threshold device (ITD). ScO2 (via near-infrared spectroscopy), MCAv and PCAv (both via transcranial Doppler ultrasound), and arterial pressure (via finger photoplethysmography) were measured continuously. Hemodynamic responses were analyzed between the Control and ITD condition at baseline (T1) and the time representing 10 s before presyncope in the Control condition (T2). While breathing on the ITD increased LBNP tolerance from 1,506 ± 75 s to 1,704 ± 88 s (P = 0.003), both mean MCAv and mean PCAv were similar between conditions at T2 (P ≥ 0.46), and decreased by the same magnitude with and without ITD breathing (P ≥ 0.53). ScO2 also decreased by ~9% with or without ITD breathing at T2 (P = 0.97), and there were also no differences in deoxygenated (dHb) or oxygenated hemoglobin (HbO2) between conditions at T2 (P ≥ 0.43). There was no evidence that protection of regional cerebral blood velocity (i.e., anterior or posterior cerebral circulation) nor cerebral oxygen extraction played a key role in the determination of tolerance to central hypovolemia with resistance breathing.

Insulin Resistance Adversely Affects Cutaneous Microvascular Perfusion Responses to Insulin Iontophoresis in Spinal Cord Injury

Insulin is a vasoactive hormone and second messenger of nitric oxide that facilitates endothelial-mediated dilatation of the microvasculature with assistance by the sympathetic nervous system (SNS). The sensitivity or resistance of endothelial-mediated mechanisms that regulate skin blood flow may play an integral role in optimizing skin perfusion in vascular beds where SNS vasomotor impairment is present. Spinal cord injury (SCI) is characterized by interruption of supraspinal SNS control of sublesional vasomotor tone. PURPOSE: To determine the effects of insulin resistance (IR) on sublesional cutaneous perfusion responses to insulin provocation in persons with SCI. METHODS: A prospective, open-label, non-randomized, placebo-controlled investigation was performed in persons with SCI and an able-bodied (AB) cohort. These groups were subdivided based on fasting plasma insulin (FPI) concentration cut-offs for IR (≥13.13 mIU/ml) or insulin sensitive (IS: <13.13 mIU/ml) designations into four subgroups: ABIS (n=21); SCIS (n=21); ABIR (n=9); SCIR (n=11). Laser Doppler flowmetry characterized the peak blood perfusion unit (BPU) responses (percent change from baseline) to insulin or placebo iontophoresis in the lower extremities, and the corresponding BPU responses were log10 transformed to facilitate comparisons. The NetIns BPU response was calculated (Insulin-Placebo BPU responses) to provide the effect of insulin to that of the acetylcholine-mediated BPU response. RESULTS: The groups were matched for demographics. By study design, FPI was different between the IS and IR subgroups. In ABIS, the BPU responses to insulin were significantly greater than placebo (p<0.05 and p<0.0001, respectively). In ABIR and SCIR, insulin did not produce a BPU response that differed from placebo. In SCIS, the insulin BPU response was greater than placebo (p<0.0001). The NetIns response was significantly greater in both IS groups compared to their corresponding IR group. CONCLUSIONS: Persons with SCI have sublesional microvascular endothelial dysfunction. The presence of IR has a further confounding effect on endothelial-mediated changes to cutaneous perfusion and appears to be an important modifiable risk factor for the optimization of cutaneous perfusion in the lower extremities of persons with SCI.

Reduction of BOLD interference in pseudo-continuous arterial spin labeling: towards quantitative fMRI

Fluctuations in blood-oxygenation level dependent (BOLD) signal and perfusion affect the quantification of changes in cerebral blood flow (CBF), coupled to neuronal activity, in arterial spin labeling (ASL). Subtraction methods for control and labeled MR images (i.e. pair-wise, surround subtraction, and subtraction of sinc-interpolated images), postulated to mitigate this interference in pseudo-continuous ASL (pCASL), were evaluated by comparison with quantitative 15O-water PET. At rest, a good agreement in the CBF values was found between PET and MRI for each of the subtraction methods. Stimulation of the visual system resulted in a regional CBF increase in the occipital lobe, which was detectable in both modalities. Bland–Altman analysis showed a systematic underestimation of the CBF values during activation in MRI. Evaluation of the relative CBF change induced by neuronal stimulation showed good inter-modality agreement for the three subtraction methods. Perfusion data obtained with each subtraction method followed the stimulation paradigm without significant differences in the correlation patterns or in the time lag between stimulation and perfusion response. Comparison to the gold standard confirmed the detectability of a neuronal stimulation pattern by pCASL. The results indicate that the combined use of background suppression and short TE reduces the BOLD-weighting in the pCASL signal.

Alterations in autonomic cerebrovascular control after spinal cord injury.

Among chronic cardiovascular and metabolic sequelae of spinal cord injury (SCI) is an up-to four-fold increase in the risk of ischemic and hemorrhagic stroke, suggesting that individuals with SCI cannot maintain stable cerebral perfusion. In able-bodied individuals, the cerebral vasculature is able to regulate cerebral perfusion in response to swings in arterial pressure (cerebral autoregulation), blood gases (cerebral vasoreactivity), and neural metabolic demand (neurovascular coupling). This ability depends, at least partly, on intact autonomic function, but high thoracic and cervical spinal cord injuries result in disruption of sympathetic and parasympathetic cerebrovascular control. In addition, alterations in autonomic and/or vascular function secondary to paralysis and physical inactivity can impact cerebrovascular function independent of the disruption of autonomic control due to injury. Thus, it is conceivable that SCI results in cerebrovascular dysfunction that may underlie an elevated risk of stroke in this population, and that rehabilitation strategies targeting this dysfunction may alleviate the long-term risk of adverse cerebrovascular events. However, despite this potential direct link between SCI and the risk of stroke, studies exploring this relationship are surprisingly scarce, and the few available studies provide equivocal results. The focus of this review is to provide an integrated overview of the available data on alterations in cerebral vascular function after SCI in humans, and to provide suggestions for future research.

Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice

AbstractNeutrophil extracellular traps (NETs; webs of DNA coated in antimicrobial proteins) are released into the vasculature during sepsis where they contribute to host defense, but also cause tissue damage and organ dysfunction. Various components of NETs have also been implicated as activators of coagulation. Using multicolor confocal intravital microscopy in mouse models of sepsis, we observed profound platelet aggregation, thrombin activation, and fibrin clot formation within (and downstream of) NETs in vivo. NETs were critical for the development of sepsis-induced intravascular coagulation regardless of the inciting bacterial stimulus (gram-negative, gram-positive, or bacterial products). Removal of NETs via DNase infusion, or in peptidylarginine deiminase-4–deficient mice (which have impaired NET production), resulted in significantly lower quantities of intravascular thrombin activity, reduced platelet aggregation, and improved microvascular perfusion. NET-induced intravascular coagulation was dependent on a collaborative interaction between histone H4 in NETs, platelets, and the release of inorganic polyphosphate. Real-time perfusion imaging revealed markedly improved microvascular perfusion in response to the blockade of NET-induced coagulation, which correlated with reduced markers of systemic intravascular coagulation and end-organ damage in septic mice. Together, these data demonstrate, for the first time in an in vivo model of infection, a dynamic NET–platelet–thrombin axis that promotes intravascular coagulation and microvascular dysfunction in sepsis.

Functional MRI for quantitative treatment response prediction in locally advanced rectal cancer.

Despite advances in multimodality treatment strategies for locally advanced rectal cancer and improvements in locoregional control, there is still a considerable variation in response to neoadjuvant chemoradiotherapy (CRT). Accurate prediction of response to neoadjuvant CRT would enable early stratification of management according to good responders and poor responders, in order to adapt treatment to improve therapeutic outcomes in rectal cancer. Clinical studies in diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI have shown promising results for the prediction of therapeutic response in rectal cancer. DWI allows for assessment of tumour cellularity. DCE-MRI enables evaluation of factors of the tumour microvascular environment and changes in perfusion in response to treatment. Studies have demonstrated that predictors of good response to CRT include lower tumour pre-CRT apparent diffusion coefficient (ADC), greater percentage increase in ADC during and post CRT, and higher pre-CRT Ktrans. However, the mean ADC and Ktrans values do not adequately reflect tumour heterogeneity. Multiparametric MRI using quantitative DWI and DCE-MRI in combination, and a histogram analysis technique can assess tumour heterogeneity and its response to treatment. This strategy has the potential to improve the accuracy of therapeutic response prediction in rectal cancer and warrants further investigation.

Microvascular reactivity to thermal stimulation in patients with diabetes mellitus and polyneuropathy.

The study aimed to investigate local thermally induced microvascular reactivity in patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM) and polyneuropathy and to compare it with healthy controls. A hundred and fourteen subjects were investigated divided into 3 groups: 1st group -20 patients with T1DM; 2nd group -50 patients with T2DM; 3rd group -44 healthy controls. The skin perfusions of the first tiptoe were monitored by laser Doppler flowmetry during thermal test. The initial (PUi) and basal perfusions at 32°C (PUb) tended to be higher in the DM groups and the PUb of T1DM group was higher compared with the healthy subjects. The perfusion responses to heating were attenuated in the patients compared with the controls. The calculated vasodilator heat-induced indices were significantly lower and the vasoconstrictor indices during relative cooling in the recovery period were significantly higher in DM patients related to the healthy subjects. The reduced cutaneous microvascular responses to local thermal stimulation in the plantar sides of the toes of both T1DM and T2DM patients with polyneuropathy were similar to those found by previous studies in other investigated sites of glabrous and nonglabrous skin of patients with DM.

Venoarteriolar reflex responses in diabetic patients.

The aim of this study was to investigate the venoarteriolar reflex (VAR) responses in type 1 (T1DM) and type 2 (T2DM) diabetes mellitus (DM) with polyneuropathy and to estimate their relationship with age, DM duration, initial cutaneous temperature and body mass index. Four groups of subjects were investigated: 1st group -20 patients with T1DM; 2nd group -50 patients with T2DM; 3rd group of 20 healthy subjects with similar age and body mass index (BMI) to the T1DM group; 4th group (Control2) of 24 healthy subjects adjusted by age and BMI to the T2DM group. The cutaneous perfusions of the big toe pulp were monitored as baseline perfusions at a temperature of 32°C in supine and sitting position with hanging legs and back in supine position. Loss of venoarteriolar reflex responses was established in 75% of T1DM patients, 78% of T2DM patients and in none of the investigated healthy controls. Reduced venoarteriolar perfusion responses were established in both T1DM and T2DM patients with polyneuropathy compared with healthy subjects. Reliable positive associations between VAR responses and the age, DM duration and initial cutaneous temperature were found.

Abstract P4-02-02: Increased tumor perfusion following treatment with trastuzumab as measured by contrast-enhanced ultrasound

Abstract Introduction: The primary purpose of this study is to determine if the order of dosing in standard-of-care (SOC) combination therapy for HER2+ breast cancer has an effect on the perfusion characteristics within the tumor. Improving the intratumoral delivery of cytotoxic systemic therapy is a significant challenge in advancing cancer treatment. Knowledge of the vascular changes following SOC treatments could enable optimizing their order and timing, potentially leading to significantly improved response. Currently, one SOC regimen for HER2+ breast cancer treatment is doxorubicin administered for 3-4 cycles prior to trastuzumab. Our goal is to quantitatively map the changes in perfusion in response to different combinations of trastuzumab plus doxorubicin treatment through imaging in a murine model of HER2+ breast cancer. Experimental Design: BT474 breast cancer cells (1×107) were subcutaneously implanted into mice (n = 12) and randomly assigned into three treatment groups: two doses of trastuzumab (10 mg/kg) followed by doxorubicin (1.5 mg/kg), doxorubicin prior to trastuzumab (same total drug dosage as group 1), and saline. After tumors reached ~225 mm3, animals were imaged with contrast-enhanced ultrasound (CEUS) (VisualSonics Vevo 770, Definity microbubbles) before treatment (day 0), and on days 1, 3, 4, and 7. Treatment occurred on days 0, 3 and 4. Percent change (from baseline, day 0 scans) of the CEUS signal intensity quantified from the functional vasculature (surrogate for vessel perfusion) following contrast injection were measured for each animal for each day. Tumors were extracted on day 7, and sectioned, paraffin-embedded, and stained with CD31, alpha-SMA and H&amp;E. Results: Tumors treated with trastuzumab initially exhibited a significant increase in CEUS signal intensity (from the functional vasculature) on day 1 compared to tumors initially treated with doxorubicin (p &amp;lt; 0.01). Additionally, compared to the control tumors, tumors treated with trastuzumab prior to doxorubicin revealed a significant increase in perfusion (change in signal intensity of functional vasculature) of contrast agent on days 3 (p = 0.01), 4 (p = 0.001) and day 7 (p &amp;lt; 0.01). There were no significant differences in the doxorubicin treated first group and the controls on any of the days (p &amp;gt; 0.25). Qualitative differences were noted between control and treated groups for alpha-SMA, no apparent differences were noted in microvessel density. Conclusion: Trastuzumab significantly improves a tumor's vascular perfusion in this HER2+ breast cancer model. Doxorubicin dosing prior to treatment with trastuzumab may potentially be hindering the intratumoral delivery of the subsequently delivered, targeted therapy. Improving the tumor's functional vasculature by altering the order of dosing of these combination therapies by giving trastuzumab prior to cytotoxic therapy has potential to enhance both the delivery and the effectiveness of these combination therapies. These data indicate a potential pathway to optimize therapeutic efficacy for individual HER2+ breast cancer patients. Citation Format: Sorace AG, Barnes SL, Quarles CC, McIntyre JO, Yankeelov TE. Increased tumor perfusion following treatment with trastuzumab as measured by contrast-enhanced ultrasound [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-02-02.

Cerebrovascular Reactivity and Intellectual Outcome in Childhood Stroke With Transient Cerebral Arteriopathy

BackgroundHypercapnic-challenge blood oxygen level–dependent magnetic resonance imaging cerebrovascular reactivity (CVR), measures the regional perfusion response to altered carbon dioxide. CVR correlates with the tissue-level microvascular dysfunction and ischemic risk. Among children with arterial ischemic stroke, transient cerebral arteriopathy (TCA) is a frequent, nonprogressive unilateral intracranial arteriopathy, which typically results in basal ganglia infarction and chronic cerebral artery stenosis. Therefore TCA provides a model for studying the consequences of chronic nonprogressive stenosis using CVR and intellectual outcome. We hypothesized that children with TCA and chronic nonprogressive intracranial artery stenosis have impaired CVR distal to the stenosis and associated cognitive impairment. MethodsWe studied children with a prior diagnosis of TCA as defined by infarction limited to the basal ganglia, internal capsule, or both; and significant (greater than 50% diameter) residual stenosis of the supraclinoid internal carotid artery, its proximal branches or both. All children had CVR, intellectual function, and infarct volumes quantified. ResultsWe performed CVR studies in five children at mean 8.96 years (3.33 to 14.58 years) poststroke. Impaired CVR was limited to the infarct zone and adjacent white matter in most children. Intellectual function was broadly average in all but one subject. ConclusionsIn children with typical TCA, ipsilateral cortical CVR and intellectual function seem to be preserved despite persistent arterial stenosis in the majority. These findings suggest that chronic revascularization strategies in these children may not be indicated and require further exploration in a larger cohort of children.

Contrast-Enhanced Ultrasound Reveals Exercise-Induced Perfusion Deficits in Claudicants.

Contrast-Enhanced Ultrasonography (CEUS) is an imaging modality allowing perfusion quantification in targeted regions of interest of the lower extremity that has not been possible with color-flow imaging or with measurement of ankle brachial indices. We developed a protocol to quantify lower extremity muscle perfusion impairment in PAD patients in response to exercise. Thirteen patients with Rutherford Class I-III Peripheral Arterial Disease (PAD) and no prior revascularization procedures were recruited from the Baltimore Veterans Affairs Medical Center and compared with eight control patients without PAD. CEUS interrogation of the index limb gastrocnemius muscle was performed using an intravenous bolus of lipid-stabilized microsphere contrast before and after a standardized treadmill protocol. Peak perfusion (PEAK) and time to peak perfusion (TTP) were measured before and after exercise. Between and within group differences were assessed. Control subjects demonstrated a more rapid TTP (p<0.01) and an increase in peak perfusion (PEAK, p=0.02) after exercise, when compared to their baseline measures. Patients with PAD demonstrated TTP and PEAK measures equivalent to controls at baseline (p=0.39, p=0.71, respectively). However, they exhibited no significant exercise-induced changes in perfusion (TTP p=0.49 and PEAK 0.67, respectively compared to baseline). After exercise, normal subjects had significantly shorter TTP (p=0.04) and greater PEAK (p=0.02) than PAD patients. Consistent with their lack of ischemic symptoms at rest, class I to III claudicant PAD patients showed similar perfusion measures (TTP and PEAK) at rest. PAD patients, however, were unable to increase perfusion in response to exercise, whereas controls increased perfusion significantly. This corresponds with claudication and limited walking capacity observed in PAD. CEUS with bolus injection offers a convenient, objective, quantitative and visual physiologic assessment of perfusion limitation in specific muscle groups of PAD patients. This has the potential for substantial clinical and research utility.

Changes of Blood Flux at BL21 and Points along BL Meridian Resulted from Acupuncture or Moxibustion: Case Cross Design Study.

Acupuncture (Acup) and moxibustion (Moxi) are commonly used interventions in clinical practice. However, the difference between Acup and moxibustion mechanisms is unclear. In current study, blood perfusion responses resulted from Acup or Moxi at Weishu acupoint (BL21) and control points were explored, respectively. The time series of blood flux signals at BL21 and control points were transformed with Morlet wavelet, and the differences in each frequency interval were observed. The results suggested that acupoint response to different stimulation is a comprehensive process which related to all components of blood perfusion signals. Whereas the different response at control points was not observed, there has been significant difference coherence value between Acup and Moxi stimulation. The results suggested the influence of Acup and Moxi not only on the level of blood perfusion at local area; the intrinsic relevance after stimulation which can be evaluated by coherence analysis is also an appropriate index to distinguish different stimulations.

Modulation of the peri-infarct neurogliovascular function by delayed COX-1 inhibition.

Stroke is the leading cause of adult disability worldwide. The absence of more effective interventions in the chronic stage-that most patients stand to benefit from-reflects uncertainty surrounding mechanisms that govern recovery. The present work investigated the effects of a novel treatment (selective cyclooxygenase-1, COX-1, inhibition) in a model of focal ischemia. FR122047 (COX-1 inhibitor) was given beginning 7 days following stroke (cortical microinjection of endothelin-1) in 23 adult male rats. Longitudinal continuous-arterial-spin-labeling was performed prior to treatment (7 days), and repeated following treatment (21 days) on a 7T magnetic resonance imaging (MRI) system to estimate resting perfusion and reactivity to hypercapnia. These in vivo measurements were buttressed by immunohistochemistry. Stroke caused an increase in perilesional resting perfusion (peri-/contralesional perfusion ratio of 170 ± 10%) and perfusion responses to hypercapnia (180 ± 10%) at 7 days. At 21 days, placebo-administered rats showed normalized perilesional perfusion (100 ± 20%) but persistent hyperreactivity (190 ± 20%). Treated animals exhibited sustained perilesional hyperperfusion (180 ± 10%). Further, reactivity lateralization did not persist following treatment (peri- vs. contralesional reactivity: P = 0.002 at 7 vs. P = 0.2 at 21 days). Hemodynamic changes were accompanied by neuronal loss, increased endothelial density, and widespread microglial and astrocytic activation. Moreover, relative to controls, treated rats showed increased perilesional neuronal survival (22 ± 1% vs. 14.9 ± 0.8%, P = 0.02) and decreased microglia/macrophage recruitment (17 ± 1% vs. 20 ± 1%, P = 0.05). Finally, perilesional perfusion was correlated with neuronal survival (slope = 0.14 ± 0.05; R2 = 0.7, P = 0.03). These findings shed light on the role of COX-1 in chronic ischemic injury and suggest that delayed selective COX-1 inhibition exerts multiple beneficial effects on the neurogliovascular unit. 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;46:505-517.

Can quantitative contrast-enhanced ultrasonography predict cervical tumor response to neoadjuvant chemotherapy?

ObjectiveTo evaluate the feasibility of quantitative contrast-enhanced ultrasonography (CEUS) for predicting and assessing cervical tumor response to neoadjuvant chemotherapy (NACT). MethodsThirty-eight cases with stage IB2 or IIA cervical cancer were studied using CEUS before and after one cycle of NACT. The quantitative CEUS parameters maximum intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (MTT) were compared between cervical tumors and myometrium (reference zone) using Sonoliver software. Absolute and relative changes in quantitative CEUS parameters were also compared among complete response, partial response, and non-responsive groups. Correlations between pre-treatment IMAX and changes in quantitative parameters were assessed after one cycle of NACT. ResultsThere were significant changes in cervical tumor IMAX (P<0.001), RT (P<0.05), and TTP (P<0.05) after one cycle of NACT. According to the Response Evaluation Criteria In Solid Tumors guidelines, the enrollments were divided into complete response, partial response, stable disease and progressive disease groups. There were no significant differences in quantitative CEUS parameters among complete response, partial response, and non-responsive groups (P>0.05). In the stable disease group (n=17), cervical tumor IMAX, RT, and TTP decreased significantly after NACT (P<0.001). The absolute and percentage changes in IMAX were positively correlated with pre-treatment IMAX in all 38 patients (r=0.576, P<0.001 and r=0.429, P<0.001). ConclusionQuantitative CEUS analysis can reveal changes in tumor perfusion following NACT. Tumor perfusion values changes likely precede size changes during the NACT course, and pre-treatment IMAX may be a valuable predictor of cervical tumor perfusion response to NACT with a great decrease in IMAX correlated with better perfusion response.

Hyperthermia and cardiovascular strain during an extreme heat exposure in young versus older adults

ABSTRACTWe examined whether older individuals experience greater levels of hyperthermia and cardiovascular strain during an extreme heat exposure compared to young adults. During a 3-hour extreme heat exposure (44°C, 30% relative humidity), we compared body heat storage, core temperature (rectal, visceral) and cardiovascular (heart rate, cardiac output, mean arterial pressure, limb blood flow) responses of young adults (n = 30, 19–28 years) against those of older adults (n = 30, 55–73 years). Direct calorimetry measured whole-body evaporative and dry heat exchange. Body heat storage was calculated as the temporal summation of heat production (indirect calorimetry) and whole-body heat loss (direct calorimetry) over the exposure period. While both groups gained a similar amount of heat in the first hour, the older adults showed an attenuated increase in evaporative heat loss (p < 0.033) in the first 30-min. Thereafter, the older adults were unable to compensate for a greater rate of heat gain (11 ± 1 ; p < 0.05) with a corresponding increase in evaporative heat loss. Older adults stored more heat (358 ± 173 kJ) relative to their younger (202 ± 92 kJ; p < 0.001) counterparts at the end of the exposure leading to greater elevations in rectal (p = 0.043) and visceral (p = 0.05) temperatures, albeit not clinically significant (rise < 0.5°C). Older adults experienced a reduction in calf blood flow (p < 0.01) with heat stress, yet no differences in cardiac output, blood pressure or heart rate. We conclude, in healthy habitually active individuals, despite no clinically observable cardiovascular or temperature changes, older adults experience greater heat gain and decreased limb perfusion in response to 3-hour heat exposure.

Quantitative MRI biomarkers to characterize regional left ventricular perfusion and function in nonhuman primates during dobutamine-induced stress: A reproducibility and reliability study.

To identify reproducible and reliable noninvasive regional imaging biomarkers of cardiac function and perfusion at rest and under stress in healthy nonhuman primates (NHPs) that may be used in the future for the early characterization of preclinical heart failure models, to evaluate therapy, and for clinical translation. Seven naive cynomolgus macaques underwent test-retest 3T cardiac MRI tagging and dual-bolus perfusion experiments. Regional cardiac function biomarkers, such as peak circumferential strain (CS), average diastolic strain-rate (DSR), contractile reserve (CR), diastolic reserve, peak torsion, and torsion reserve were quantified. Further, regional myocardial blood flow (MBF), myocardial perfusion reserve (MPR), and myocardial perfusion reserve-to-contractile reserve (MPR/CR) were also derived. Inter- and intraobserver reproducibility and test-retest reliability analyses were conducted using the reliability and generalizability coefficients including correlation coefficient (CC) and intraclass correlation coefficient (ICC). Overall, peak CS, DSR, and MBF are robust biomarkers at both rest and stress with moderate-good inter- and intraobserver reproducibility and test-retest reliability. At rest: intra-/interobserver reproducibility (CC): peak CS (0.81/0.81), DSR (0.81/0.81), MBF (0.72/0.57), peak torsion (0.79/0.79); test-retest reliability: (CC/ICC): peak CS (0.62/0.75), DSR (0.24/0.55), MBF (0.66/0.62), and peak torsion (0.79/0.78). Under stress: intra-/interobserver reproducibility (CC): peak CS (0.61/0.60), DSR (0.50/0.50), MBF (0.63/0.61), MPR (0.43/0.43), and peak torsion (0.38/0.38); test-retest reliability: (CC/ICC): peak CS (0.58/0.58), DSR (0.24/0.43), MBF (0.58/0.58), MPR (0.43/0.38), and peak torsion (0.38/0.38). We demonstrated the feasibility of using cardiac MRI to characterize left ventricular functional and perfusion responses to stress in an NHP species, and specific robust biomarkers such as peak CS, DSR, MBF, diastolic reserve, and MPR have been identified for clinical translation and drug research. 1 J. Magn. Reson. Imaging 2017;45:556-569.

Evaluating Instantaneous Perfusion Responses of Parotid Glands to Gustatory Stimulation Using High-Temporal-Resolution Echo-Planar Diffusion-Weighted Imaging.

Parotid glands secrete and empty saliva into the oral cavity rapidly after gustatory stimulation. However, the role of the temporal resolution of DWI in investigating parotid gland function remains uncertain. Our aim was to design a high-temporal-resolution echo-planar DWI pulse sequence and to evaluate the instantaneous MR perfusion responses of the parotid glands to gustatory stimulation. This prospective study enrolled 21 healthy volunteers (M/F = 2:1; mean age, 45.2 ± 12.9 years). All participants underwent echo-planar DWI (total scan time, 304 seconds; temporal resolution, 4 s/scan) on a 1.5T MR imaging scanner. T2WI (b = 0 s/mm2) and DWI (b = 200 s/mm2) were qualitatively assessed. Signal intensity of the parotid glands on T2WI, DWI, and ADC was quantitatively analyzed. One-way ANOVA with post hoc group comparisons with Bonferroni correction was used for statistical analysis. P < .05 was statistically significant. Almost perfect interobserver agreement was achieved (κ ≥ 0.656). The parotid glands had magnetic susceptibility artifacts in 14.3% (3 of 21) of volunteers during swallowing on DWI but were free from perceptible artifacts at the baseline and at the end of scans on all images. Increased ADC and reduced signal intensity of the parotid glands on T2WI and DWI occurred immediately after oral administration of lemon juice. Maximal signal change of ADC (24.8% ± 10.8%) was significantly higher than that of T2WI (-10.1% ± 5.2%, P < .001). The recovery ratio of ADC (100.71% ± 42.34%) was also significantly higher than that of T2WI (22.36% ± 15.54%, P < .001). Instantaneous parotid perfusion responses to gustatory stimulation can be quantified by ADC by using high-temporal-resolution echo-planar DWI.

Intraoperative monitoring of blood perfusion in port wine stains by laser Doppler imaging during vascular targeted photodynamic therapy: A preliminary study

ObjectiveThe objective of this study was to monitor blood perfusion dynamics of port wine stains (PWS) during vascular targeted photodynamic therapy (V-PDT) with laser Doppler imaging (LDI). MethodsThe PWS lesions of 30 facial PWS patients received V-PDT, while the normal skins on the forearm of 5 healthy subjects were treated as light-only controls for comparison. Furthermore, two different PWS lesions in the same individual from each of 3 PWS patients successively received laser irradiation only and V-PDT, respectively. LDI was used to monitor intraoperative blood perfusion dynamics. ResultsDuring V-PDT, the blood perfusion (278±96 PU) in PWS lesions for 31 of 33 PWS patients significantly increased after the initiation of V-PDT treatment, then reached a peak (638±105 PU) within 10min, followed by a slow decrease to a relatively lower level (515±100 PU). Furthermore, the time for reaching peak and the subsequent magnitude of decrease in blood perfusion varied with different patients. For light-only controls, an initial perfusion peak at 3min followed by a nadir and a secondary increase were found not only in normal skin, but also in PWS lesions. ConclusionThe preliminary results showed that the LDI permits non-invasive monitoring blood perfusion changes of PWS lesions during V-PDT. There was a clear trend in blood perfusion responses during V-PDT and laser irradiation. The blood perfusion changes during treatment were due to V-PDT effects as well as local temperature increase induced by laser irradiation.