Deep learning of image-derived measures of body composition in pediatric, adolescent, and young adult lymphoma: association with late treatment effects.

OBJECTIVES: The objective of this study was to translate a deep learning (DL) approach for semiautomated analysis of body composition (BC) measures from standard of care CT images to investigate the prognostic value of BC in pediatric, adolescent, and young adult (AYA) patients with lymphoma. METHODS: This 10-year retrospective, single-site study of 110 pediatric and AYA patients with lymphoma involved manual segmentation of fat and muscle tissue from 260 CT imaging datasets obtained as part of routine imaging at initial staging and first therapeutic follow-up. A DL model was trained to perform semiautomated image segmentation of adipose and muscle tissue. The association between BC measures and the occurrence of 3-year late effects was evaluated using Cox proportional hazards regression analyses. RESULTS: DL-guided measures of BC were in close agreement with those obtained by a human rater, as demonstrated by high Dice scores (≥ 0.95) and correlations (r > 0.99) for each tissue of interest. Cox proportional hazards regression analyses revealed that patients with elevated subcutaneous adipose tissue at baseline and first follow-up, along with patients who possessed lower volumes of skeletal muscle at first follow-up, have increased risk of late effects compared to their peers. CONCLUSIONS: DL provides rapid and accurate quantification of image-derived measures of BC that are associated with risk for treatment-related late effects in pediatric and AYA patients with lymphoma. Image-based monitoring of BC measures may enhance future opportunities for personalized medicine for children with lymphoma by identifying patients at the highest risk for late effects of treatment. KEY POINTS: • Deep learning-guided CT image analysis of body composition measures achieved high agreement level with manual image analysis. • Pediatric patients with more fat and less muscle during the course of cancer treatment were more likely to experience a serious adverse event compared to their clinical counterparts. • Deep learning of body composition may add value to routine CT imaging by offering real-time monitoring of pediatric, adolescent, and young adults at high risk for late effects of cancer treatment.

Quantification of chemotherapy-induced changes in body composition in pediatric, adolescent, and young adult lymphoma using standard of care CT imaging.

OBJECTIVES: The objective of this study was to use computed tomography (CT) imaging to quantify chemotherapy-induced changes in body composition (BC) in pediatric, adolescent, and young adult (AYA) patients with lymphoma and to compare image-derived changes in BC measures to changes in traditional body mass index (BMI) measures. METHODS: Skeletal muscle (SkM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) volumes were manually segmented using low-dose CT images acquired from a 10-year retrospective, single-site cohort of 110 patients with lymphoma. CT images and BMI percentiles (BMI%) were acquired from baseline and first therapeutic follow-up. CT image segmentation was performed at vertebral level L3 using 5 consecutive axial CT images. RESULTS: CT imaging detected significant treatment-induced changes in BC measures from baseline to first follow-up time points, with SAT and VAT significantly increasing and SkM significantly decreasing. BMI% measures did not change from baseline to first follow-up and were not significantly correlated with changes in image-derived BC measures. Patients who were male, younger than 12 years old, diagnosed with non-Hodgkin's lymphoma, and presented with stage 3 or 4 disease gained more adipose tissue and lost more SkM in response to the first cycle of treatment compared to their clinical counterparts. CONCLUSIONS: Standard of care CT imaging can quantify treatment-induced changes in BC that are not reflected by traditional BMI assessment. Image-based monitoring of BC parameters may offer personalized approaches to lymphoma treatment for pediatric and AYA patients by guiding cancer treatment recommendations and subsequently enhance clinical outcomes. KEY POINTS: • Standard of care low-dose CT imaging quantifies chemotherapy-induced changes in body composition in pediatric, adolescent, and young adults with lymphoma. • Body mass index could not detect changes in body composition during treatment that were quantified by CT imaging. • Pediatric and AYA patients who were male, younger than 12 years old, and diagnosed with non-Hodgkin's lymphoma, and presented with stage 3 or 4 disease gained more adipose tissue and lost more skeletal muscle tissue in response to the first cycle of treatment compared to their clinical counterparts.

SPECT/CT imaging of lower extremity perfusion reserve: A non-invasive correlate to exercise tolerance and cardiovascular fitness in patients undergoing clinically indicated myocardial perfusion imaging.

BACKGROUND: Although exercise is often prescribed for the management of cardiovascular diseases, a non-invasive imaging approach that quantifies skeletal muscle physiology and correlates with patients' functional capacity and cardiovascular fitness has been absent. Therefore, we evaluated the potential of lower extremity single photon emission computed tomography (SPECT)/CT perfusion imaging as a non-invasive correlate to exercise tolerance and cardiovascular fitness. METHODS: Patients (n = 31) undergoing SPECT/CT myocardial perfusion imaging underwent additional stress/rest SPECT/CT imaging of the lower extremities. CT-based image segmentation was used for regional quantification of perfusion reserve within the tibialis anterior, soleus, and gastrocnemius muscles. Metabolic equivalents (METs) at peak exercise and heart rate recovery (HRR) after exercise were recorded. RESULTS: Peak METs were significantly associated with perfusion reserve of tibialis anterior (p = 0.02), soleus (p = 0.01) and gastrocnemius (p = 0.01). HRR was significantly associated with perfusion reserve of the soleus (p = 0.02) and gastrocnemius (p = 0.04) muscles. Perfusion reserve of the tibialis anterior (40.6 ± 20.2%), soleus (35.4 ± 16.7%), and gastrocnemius (29.7 ± 19.1%) all significantly differed from each other. CONCLUSIONS: SPECT/CT imaging provides regional quantification of skeletal muscle perfusion reserve which is significantly associated with exercise tolerance and cardiovascular fitness. Future application of SPECT/CT may elucidate the underlying skeletal muscle adapations to exercise therapy in patients with cardiovascular diseases.

Prolonged sitting negatively affects the postprandial plasma triglyceride-lowering effect of acute exercise.

The interaction of prolonged sitting with physical exercise for maintaining health is unclear. We tested the hypothesis that prolonged siting would have a deleterious effect on postprandial plasma lipemia (PPL, postprandial plasma triglycerides) and reduce the ability of an acute exercise bout to attenuate PPL. Seven healthy young men performed three, 5-day interventions [days 1-5 (D1-D5)] in a randomized crossover design with >1 wk between interventions: 1) sitting > 14 h/day with hypercaloric energy balance (SH), 2) sitting >14 h/day with net energy balance (SB), and 3) active walking/standing with net energy balance (WB) and sitting 8.4 h/day. The first high-fat tolerance test (HFTT1) was performed on D3 following 2 days of respective interventions. On the evening of D4 subjects ran on a treadmill for 1 h at ~67% V̇o2max, followed by the second HFTT (HFTT2) on D5. Two days of prolonged sitting increased TG AUCI (i.e., incremental area under the curve for TG), irrespective of energy balance, compared with WB (27% in SH, P = 0.003 and 26% in SB, P = 0.046). Surprisingly, after 4 days of prolonged sitting (i.e.; SH and SB), the acute exercise on D4 failed to attenuate TG AUCI or increase relative fat oxidation in HFTT2, compared with HFTT1, regardless of energy balance. In conclusion, prolonged sitting over 2-4 days was sufficient to amplify PPL, which was not attenuated by acute exercise, regardless of energy balance. This underscores the importance of limiting sitting time even in people who have exercised.

Quantification of Skeletal Muscle Perfusion in Peripheral Artery Disease Using 18F-Sodium Fluoride Positron Emission Tomography Imaging.

BACKGROUND: Perfusion deficits contribute to symptom severity, morbidity, and death in peripheral artery disease (PAD); however, no standard method for quantifying absolute measures of skeletal muscle perfusion exists. This study sought to preclinically test and clinically translate a positron emission tomography (PET) imaging approach using an atherosclerosis-targeted radionuclide, fluorine-18-sodium fluoride (18F-NaF), to quantify absolute perfusion in PAD. METHODS AND RESULTS: Eight Yorkshire pigs underwent unilateral femoral artery ligation and dynamic 18F-NaF PET/computed tomography imaging on the day of and 2 weeks after occlusion. Following 2-week imaging, calf muscles were harvested to quantify microvascular density. PET methodology was validated with microspheres in 4 additional pig studies and translated to patients with PAD (n=39) to quantify differences in calf perfusion across clinical symptoms/stages and perfusion responses in a case of revascularization. Associations between PET perfusion, ankle-brachial index, toe-brachial index, and toe pressure were assessed in relation to symptoms. 18F-NaF PET/computed tomography quantified significant deficits in calf perfusion in pigs following arterial occlusion and perfusion recovery 2 weeks after occlusion that coincided with increased muscle microvascular density. Additional studies confirmed that PET-derived perfusion measures agreed with microsphere-derived perfusion measures. Translation of imaging methods demonstrated significant decreases in calf perfusion with increasing severity of PAD and quantified perfusion responses to revascularization. Perfusion measures were also significantly associated with symptom severity, whereas traditional hemodynamic measures were not. CONCLUSIONS: 18F-NaF PET imaging quantifies perfusion deficits that correspond to clinical stages of PAD and represents a novel perfusion imaging strategy that could be partnered with atherosclerosis-targeted 18F-NaF PET imaging using a single radioisotope injection. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03622359.

Tissue engineered vascular grafts are resistant to the formation of dystrophic calcification.

Advancements in congenital heart surgery have heightened the importance of durable biomaterials for adult survivors. Dystrophic calcification poses a significant risk to the long-term viability of prosthetic biomaterials in these procedures. Herein, we describe the natural history of calcification in the most frequently used vascular conduits, expanded polytetrafluoroethylene grafts. Through a retrospective clinical study and an ovine model, we compare the degree of calcification between tissue-engineered vascular grafts and polytetrafluoroethylene grafts. Results indicate superior durability in tissue-engineered vascular grafts, displaying reduced late-term calcification in both clinical studies (p < 0.001) and animal models (p < 0.0001). Further assessments of graft compliance reveal that tissue-engineered vascular grafts maintain greater compliance (p < 0.0001) and distensibility (p < 0.001) than polytetrafluoroethylene grafts. These properties improve graft hemodynamic performance, as validated through computational fluid dynamics simulations. We demonstrate the promise of tissue engineered vascular grafts, remaining compliant and distensible while resisting long-term calcification, to enhance the long-term success of congenital heart surgeries.

Cardiovascular responses to hot skin at rest and during exercise.

Integrative cardiovascular responses to heat stress during endurance exercise depend on various variables, such as thermal stress and exercise intensity. This review addresses how increases in skin temperature alter and challenge the integrative cardiovascular system during upright submaximal endurance exercise, especially when skin is hot (i.e. >38°C). Current evidence suggests that exercise intensity plays a significant role in cardiovascular responses to hot skin during exercise. At rest and during mild intensity exercise, hot skin increases skin blood flow and abolishes cutaneous venous tone, which causes blood pooling in the skin while having little impact on stroke volume and thus cardiac output is increased with an increase in heart rate. When the heart rate is at relatively low levels, small increases in heart rate, skin blood flow, and cutaneous venous volume do not compromise stroke volume, so cardiac output can increase to fulfill the demands for maintaining blood pressure, heat dissipation, and the exercising muscle. On the contrary, during more intense exercise, hot skin does not abolish exercise-induced cutaneous venoconstriction possibly due to high sympathetic nerve activities; thus, it does not cause blood pooling in the skin. However, hot skin reduces stroke volume, which is associated with a decrease in ventricular filling time caused by an increase in heart rate. When the heart rate is high during moderate or intense exercise, even a slight reduction in ventricular filling time lowers stroke volume. Cardiac output is therefore not elevated when skin is hot during moderate intensity exercise.

Detection of multivessel calcific disease progression in a patient with chronic limb-threatening ischemia using fluorine-18 sodium fluoride positron emission tomography imaging.

Vascular calcification contributes to morbidity and poor clinical outcomes for patients with peripheral artery disease; however, the traditional assessment of the calcium burden using computed tomography (CT) imaging or angiography represents already established disease. In the present report, we describe a 69-year-old man with chronic limb-threatening ischemia who had undergone positron emission tomography/CT imaging with fluorine-18 sodium fluoride to evaluate the relationship between baseline levels of positron emission tomography-detectable active vascular microcalcification and CT-detectable calcium progression 1.5 years later. CT imaging at follow-up identified progression of existing lesions and the formation of new calcium in multiple arteries that had demonstrated elevated fluorine-18 sodium fluoride uptake 1.5 years earlier.

Vessel-by-vessel analysis of lower extremity 18F-NaF PET/CT imaging quantifies diabetes- and chronic kidney disease-induced active microcalcification in patients with peripheral arterial disease.

BACKGROUND: Positron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 (18F)-sodium fluoride (NaF) provides assessment of active vascular microcalcification, but its utility for evaluating diabetes mellitus (DM)- and chronic kidney disease (CKD)-induced atherosclerosis in peripheral arterial disease (PAD) has not been comprehensively evaluated. This study sought to use 18F-NaF PET/CT to quantify and compare active microcalcification on an artery-by-artery basis in healthy subjects, PAD patients with or without DM, and PAD patients with or without CKD. Additionally, we evaluated the contributions of DM, CKD, statin use and established CT-detectable calcium to 18F-NaF uptake for each lower extremity artery. METHODS: PAD patients (n = 48) and healthy controls (n = 8) underwent lower extremity 18F-NaF PET/CT imaging. Fused PET/CT images guided segmentation of arteries of interest (i.e., femoral-popliteal, anterior tibial, tibioperoneal trunk, posterior tibial, and peroneal) and quantification of 18F-NaF uptake. 18F-NaF uptake was assessed for each artery and compared between subject groups. Additionally, established calcium burden was quantified for each artery using CT calcium mass score. Univariate and multivariate analyses were performed to evaluate DM, CKD, statin use, and CT calcium mass as predictors of 18F-NaF uptake in PAD. RESULTS: PAD patients with DM or CKD demonstrated significantly higher active microcalcification (i.e., 18F-NaF uptake) for all arteries when compared to PAD patients without DM or CKD. Univariate and multivariate analyses revealed that concomitant DM or CKD was associated with increased microcalcification for all arteries of interest and this increased disease risk remained significant after adjusting for patient age, sex, and body mass index. Statin use was only associated with decreased microcalcification for the femoral-popliteal artery in multivariate analyses. Established CT-detectable calcium was not significantly associated with 18F-NaF uptake for 4 out of 5 arteries of interest. CONCLUSIONS: 18F-NaF PET/CT imaging quantifies vessel-specific active microcalcification in PAD that is increased in multiple lower extremity arteries by DM and CKD and decreased in the femoral-popliteal artery by statin use. 18F-NaF PET imaging is complementary to and largely independent of established CT-detectable arterial calcification. 18F-NaF PET/CT imaging may provide an approach for non-invasively quantifying vessel-specific responses to emerging anti-atherogenic therapies or CKD treatment in patients with PAD.

Vessel-by-Vessel Computed Tomography Calcium Scoring of the Foot in Peripheral Artery Disease: Association with Patient-Level Factors.

Objective: Peripheral artery disease (PAD) is associated with increased risk of nonhealing ulcers, amputation, and mortality due to occlusive atherosclerotic plaques. Computed tomography (CT) imaging detects vascular calcification in PAD; however, quantitative vessel-by-vessel analysis of calcium burden in the feet of PAD patients has not been assessed. This study sought to perform quantitative analysis of vessel-specific calcium burden and examine the patient-level determinants of foot calcium burden in PAD patients. Approach: PAD patients (n = 41) were prospectively enrolled and underwent CT imaging of the lower extremities. Manual segmentation of the medial plantar, lateral plantar, and dorsalis pedis arteries was performed. CT image Hounsfield units (HUs) were obtained for each artery to quantify vessel-by-vessel calcium mass using a cutoff value of ≥130 HU. Univariate analyses were performed to evaluate patient-level determinants of calcium burden for each foot artery. STROBE guidelines were used for reporting of data. Results: Univariate analyses revealed that body mass index, diabetes mellitus (DM), and chronic kidney disease (CKD) were significant determinants of foot calcium burden in PAD patients. Image analysis demonstrated that PAD patients with DM had significantly higher calcium mass for the medial plantar (p = 0.005), lateral plantar (p = 0.039), and dorsalis pedis (p = 0.001) arteries compared with PAD patients without DM. Innovation: This is the first study to use CT imaging to quantify vessel-specific calcium burden in the feet of patients with PAD and evaluate the patient-level determinants of foot calcium burden in the setting of PAD. Conclusion: CT imaging quantifies vessel-specific calcification in the feet of PAD patients, which is exacerbated with concomitant DM, CKD, and/or obesity.

Prognostic Value of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging for Predicting Venous Thromboembolism in Children With Lymphoma.

BACKGROUND: Positron emission tomography (PET)/computed tomography (CT) imaging can detect changes in arterial inflammation, but has not been used to evaluate chemotherapy-induced venous inflammation or assess risk for venous thromboembolism (VTE) in pediatric oncology. Therefore, the purpose of this study was to evaluate the prognostic value of fluorine-18-fluorodeoxyglucose PET/CT imaging of venous inflammation for predicting VTE occurrence in the 12 months after lymphoma diagnosis in pediatric, adolescent, and young adult patients. METHODS: Pediatric, adolescent, and young adult patients with lymphoma diagnoses (n=71) who underwent whole-body PET/CT imaging at initial staging of disease and first therapeutic follow-up were retrospectively evaluated for serial changes in lower extremity venous uptake of fluorine-18-fluorodeoxyglucose. PET/CT images were used to segment and quantify serial changes in fluorine-18-fluorodeoxyglucose uptake for veins of interest (ie, popliteal and femoral). Incidence of VTE was assessed for 12 months after lymphoma diagnosis. RESULTS: PET/CT detected a significantly higher inflammatory response in the femoral (P=0.012) and popliteal (P=0.013) veins of patients who experienced a VTE event compared with those who remained VTE free in the 12 months after diagnosis. The area under the curve values for receiver operator characteristics analyses were 0.76 (femoral vein) and 0.77 (popliteal vein) based on incidence of VTE occurrence. Univariate analyses demonstrated that PET/CT-derived changes in femoral (P=0.008) and popliteal (P=0.002) vein inflammation were significantly associated with VTE-free survival at 12 months after diagnosis. CONCLUSIONS: Fluorine-18-fluorodeoxyglucose PET/CT imaging detects treatment-induced venous toxicity that may provide insight into risk of VTE events in pediatric and adolescent and young adult patients with lymphoma.

Novel Application of 18F-NaF PET/CT Imaging for Evaluation of Active Bone Remodeling in Diabetic Patients With Charcot Neuropathy: A Proof-of-Concept Report.

Charcot neuropathic osteoarthropathy (CN) is a serious and potentially limb-threatening complication for patients with diabetes mellitus and peripheral arterial disease. In recent decades, nuclear medicine-based approaches have been used for non-invasive detection of CN; however, to date, a positron emission tomography (PET) radionuclide specifically focused on targeted imaging of active bone remodeling has not been explored or validated for patients with CN. The radionuclide 18F-sodium fluoride (NaF) has historically been used as a bone imaging probe due to its high sensitivity for targeting hydroxyapatite and bone turnover, but has not been applied in the context of CN. Therefore, the present study focused on novel application of 18F-NaF PET/computed tomography (CT) imaging to three clinical cases of CN to evaluate active bone remodeling at various time courses of CN. PET/CT imaging in all 3 cases demonstrated focal uptake of 18F-NaF in the bones of the feet afflicted with CN, with bone retention of 18F-NaF persisting for up to 5 years following surgical reconstruction of the foot in two cases. On a group level, 18F-NaF bone uptake in the CN foot was significantly higher compared to the healthy, non-CN foot (p = 0.039). 18F-NaF PET/CT imaging may provide a non-invasive tool for monitoring active bone remodeling in the setting of CN, thereby offering novel opportunities for tracking disease progression and improving treatment and surgical intervention.

Prognostic Value of Radiotracer-Based Perfusion Imaging in Critical Limb Ischemia Patients Undergoing Lower Extremity Revascularization.

OBJECTIVES: The purpose of this study was to evaluate the prognostic value of single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of angiosome foot perfusion for predicting amputation outcomes in patients with critical limb ischemia (CLI) and diabetes mellitus (DM). BACKGROUND: Radiotracer imaging can assess microvascular foot perfusion and identify regional perfusion abnormalities in patients with critical limb ischemia CLI and DM, but the relationship between perfusion response to revascularization and subsequent clinical outcomes has not been evaluated. METHODS: Patients with CLI, DM, and nonhealing foot ulcers (n = 25) were prospectively enrolled for SPECT/CT perfusion imaging of the feet before and after revascularization. CT images were used to segment angiosomes (i.e., 3-dimensional vascular territories) of the foot. Relative changes in radiotracer uptake after revascularization were evaluated within the ulcerated angiosome. Incidence of amputation was assessed at 3 and 12 months after revascularization. RESULTS: SPECT/CT detected a significantly lower microvascular perfusion response for patients who underwent amputation compared with those who remained amputation free at 3 (p = 0.01) and 12 (p = 0.01) months after revascularization. The cutoff percent change in perfusion for predicting amputation at 3 months was 7.55%, and 11.56% at 12 months. The area under the curve based on the amputation outcome was 0.799 at 3 months and 0.833 at 12 months. The probability of amputation-free survival was significantly higher at 3 (p = 0.002) and 12 months (p = 0.03) for high-perfusion responders than low-perfusion responders to revascularization. CONCLUSIONS: SPECT/CT imaging detects regional perfusion responses to lower extremity revascularization and provides prognostic value in patients with CLI (Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease; NCT03622359).

Clinical Applications for Radiotracer Imaging of Lower Extremity Peripheral Arterial Disease and Critical Limb Ischemia.

Peripheral arterial disease (PAD) is an atherosclerotic occlusive disease of the non-coronary vessels that is characterized by lower extremity tissue ischemia, claudication, increased prevalence of lower extremity wounds and amputations, and impaired quality of life. Critical limb ischemia (CLI) represents the severe stage of PAD and is associated with additional risk for wound formation, amputation, and premature death. Standard clinical tools utilized for assessing PAD and CLI primarily focus on anatomical evaluation of peripheral vascular lesions or hemodynamic assessment of the peripheral circulation. Evaluation of underlying pathophysiology has traditionally been achieved by radiotracer-based imaging, with many clinical investigations focusing on imaging of skeletal muscle perfusion and cases of foot infection/inflammation such as osteomyelitis and Charcot neuropathic osteoarthropathy. As advancements in hybrid imaging systems and radiotracers continue to evolve, opportunities for molecular imaging of PAD and CLI are also emerging that may offer novel insight into associated complications such as peripheral atherosclerosis, alterations in skeletal muscle metabolism, and peripheral neuropathy. This review summarizes the pros and cons of radiotracer-based techniques that have been utilized in the clinical environment for evaluating lower extremity ischemia and common pathologies associated with PAD and CLI.

Noninvasive Detection of Active Microcalcification in an Occlusive Peripheral Vascular Aneurysm Using 18F-NaF PET/CT Imaging.

A 65-year-old man with an occluded popliteal artery aneurysm and calf claudication underwent PET/CT imaging with F-NaF to assess the status of active microcalcification in the aneurysm site and additional lower extremity arteries. CT imaging revealed macrocalcification of the aneurysm that colocalized with elevated retention of F-NaF on PET images. PET/CT detected additional distal arterial sites with focal uptake of F-NaF that did not coincide with CT-detectable macrocalcification. This report highlights a case of active microcalcification in an occlusive peripheral aneurysm using PET/CT. PET/CT may provide molecular insight into the remodeling of lower extremity aneurysms and atherosclerotic lesions.

SPECT/CT Imaging: A Noninvasive Approach for Evaluating Serial Changes in Angiosome Foot Perfusion in Critical Limb Ischemia.

Objective: To investigate the feasibility of serial radiotracer-based imaging as a noninvasive approach for quantifying volumetric changes in microvascular perfusion within angiosomes of the foot following lower extremity revascularization in the setting of critical limb ischemia (CLI). Approach: A CLI patient with a nonhealing foot ulcer underwent single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of the feet before and after balloon angioplasty of the superficial femoral artery (SFA) and popliteal artery. SPECT/CT imaging was used to evaluate serial changes in angiosome perfusion, which was compared to quantitative changes in peripheral vascular anatomy and hemodynamics, as assessed by standard clinical tools that included digital subtraction angiography (DSA), ankle-brachial index (ABI), and toe-brachial index (TBI). Results: Following revascularization, upstream quantitative improvements in stenosis of the SFA (pre: 35.4% to post: 11.9%) and popliteal artery (pre: 59.1% to post: 21.7%) shown by DSA were associated with downstream angiosome-dependent improvements in SPECT microvascular foot perfusion that ranged from 2% to 16%. ABI measurement was not possible due to extensive arterial calcification, while TBI values decreased from 0.26 to 0.16 following revascularization. Innovation: This is the first study to demonstrate the feasibility of assessing noninvasive volumetric changes in angiosome foot perfusion in response to lower extremity revascularization in a patient with CLI by utilizing radiotracer-based imaging. Conclusion: SPECT/CT imaging allows for quantification of serial perfusion changes within angiosomes containing nonhealing ulcers and provides physiological assessment that is complementary to conventional anatomical (DSA) and hemodynamic (ABI/TBI) measures in the evaluation of lower extremity revascularization.

Low Stroke Volume during Exercise with Hot Skin Is Due to Elevated Heart Rate.

It is well known that hyperthermia lowers stroke volume (SV) during moderate-intensity prolonged exercise, yet the underlying mechanism is inconclusive, especially when skin temperature (Tsk) is hot (≥38°C). PURPOSE: In the present study, HR was independently lowered by a low dose of ß1-blockade (ßB) to investigate its effect on SV during exercise when skin is hot. The effect of rapid skin cooling on reversing cardiovascular responses was also examined. METHODS: Nine men cycled at 62% V˙O2peak wearing a water-perfused suit for 20 min during three conditions: (a) moderate Tsk (~33°C) (MOD), (b) hot Tsk (~38°C) (HOT), and (c) hot Tsk (38°C) with ßB (HOT-ßB). Skin temperature was then rapidly cooled at 20 min in all trials by cold water (0°C-2°C) perfusion while subjects continued cycling for another 20 min. RESULTS: When HR was lowered during HOT-ßB (152 ± 4 bpm) to the same level as MOD (150 ± 4 bpm; P = 0.30), SV in HOT-ßB (132 ± 8 mL) was also restored to the same level as MOD (129 ± 7 mL, P = 0.37) even with a significantly higher cutaneous blood flow (CBF) and lower mean arterial blood pressure. When Tsk was rapidly cooled, cardiac output, HR, and CBF significantly decreased while SV remained lower in HOT. Forearm venous volume was not different between trials during heating and cooling. CONCLUSIONS: The increase in HR rather than an increase in CBF or forearm venous volume was responsible for the decrease in SV during moderate-intensity exercise when Tsk was held at 38°C.

Cardiovascular responses to exercise when increasing skin temperature with narrowing of the core-to-skin temperature gradient.

The decline in stroke volume (SV) during exercise in the heat has been attributed to either an increase in cutaneous blood flow (CBF) that reduces venous return or an increase in heart rate (HR) that reduces cardiac filling time. However, the evidence supporting each mechanism arises under experimental conditions with different skin temperatures (Tsk; e.g., ≥38°C vs. ≤36°C, respectively). We systematically studied cardiovascular responses to progressively increased Tsk (32°C-39°C) with narrowing of the core-to-skin gradient during moderate intensity exercise. Eight men cycled at 63 ± 1% peak oxygen consumption for 20-30 min. Tsk was manipulated by having subjects wear a water-perfused suit that covered most of the body and maintained Tsk that was significantly different between trials and averaged 32.4 ± 0.2, 35.5 ± 0.1, 37.5 ± 0.1, and 39.5 ± 0.1°C, respectively. The graded heating of Tsk ultimately produced a graded elevation of esophageal temperature (Tes) at the end of exercise. Incrementally increasing Tsk resulted in a graded increase in HR and a graded decrease in SV. CBF reached a similar average plateau value in all trials when Tes was above ~38°C, independent of Tsk. Tsk had no apparent effect on forearm venous volume (FVV). In conclusion, the CBF and FVV responses suggest no further pooling of blood in the skin when Tsk is increased from 32.4°C to 39.5°C. The decrease in SV during moderate intensity exercise when heating the skin to high levels appears related to an increase in HR and not an increase in CBF. NEW & NOTEWORTHY This study systematically investigated the effect of increasing skin temperature (Tsk) to high levels on cardiovascular responses during moderate intensity exercise. We conclude that the declines in stroke volume were related to the increases in heart rate but not the changes in cutaneous blood flow (CBF) and forearm venous volume (FVV) during moderate intensity exercise when Tsk increased from ~32°C to ~39°C. High Tsk (≥38°C) did not further elevate CBF and FVV compared with lower Tsk during moderate intensity exercise.

Postexercise macronutrient intake and subsequent postprandial triglyceride metabolism.

UNLABELLED: Acute endurance exercise has been shown to lower postprandial plasma triglyceride (PPTG) concentrations; however, whether this is due to the negative energy and/or CHO deficit from the exercise bout is not well understood. PURPOSE: This study aimed to examine the effects of a postexercise meal consisting of either high or low CHO content on PPTG and postprandial fat oxidation the morning after an exercise bout. METHODS: Healthy young men (n = 6) performed each of four experimental treatments: 1) nonexercise control (CON), 2) 80 min of cycling with either no meal replacement (EX), 3) a high-CHO postexercise meal (EX+HCHO), or a 4) low-CHO postexercise meal (EX+LCHO). A standardized meal for PPTG determination was provided (16.0 kcal · kg(-1) body mass, 1.02 g fa t · kg(-1), 1.36 g CHO · kg(-1), 0.31 g protein · kg(-1)) 12 h after the exercise, and measurements of plasma triglyceride (TG) concentration and whole-body resting fat oxidation were made in the fasted condition and during the 4-h postprandial period. RESULTS: The total area under the curve for plasma TG was significantly lower in EX+LCHO (325 (63) mg · dL(-1) per 4 h) compared with that in EX+HCHO (449 (118) mg · dL(-1) per 4 h, P = 0.03). Postprandial fat oxidation during this period was significantly greater in EX+LCHO (257 (58) kcal per 4 h, P = 0.003) compared with that in EX+HCHO (209 (56) kcal per 4 h). The change in total postprandial fat oxidation (kcal per 4 h) relative to CON was significantly and inversely correlated with the change in the total TG area under the curve relative to CON (mg · dL(-1) per 4 h, ΔTG AUC, R2 = 0.37, P = 0.008). CONCLUSIONS: The low CHO composition of the postexercise meal contributes to lower PPTG and increased fat oxidation, with lower PPTG related to an increase in fat oxidation.