Microvascular oxygen consumption during sickle cell pain crisis.

Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. Microvascular oxygen consumption was greater in sickle cell patients than in healthy individuals (median [interquartile range]; sickle cell: 0.91 [0.75-1.07] vs healthy: 0.75 [0.62-0.94] -ΔHbO2/min, P < .05) and was elevated further during acute pain crisis (crisis: 1.10 [0.78-1.30] vs recovered: 0.88 [0.76-1.03] -ΔHbO2/min, P < .05). Increased microvascular oxygen consumption during pain crisis could affect the local oxygen saturation of hemoglobin when oxygen delivery is limiting. Identifying the mechanisms of elevated oxygen consumption during pain crisis might lead to the development of new therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT01568710.

Ultrathin conformal devices for precise and continuous thermal characterization of human skin.

Precision thermometry of the skin can, together with other measurements, provide clinically relevant information about cardiovascular health, cognitive state, malignancy and many other important aspects of human physiology. Here, we introduce an ultrathin, compliant skin-like sensor/actuator technology that can pliably laminate onto the epidermis to provide continuous, accurate thermal characterizations that are unavailable with other methods. Examples include non-invasive spatial mapping of skin temperature with millikelvin precision, and simultaneous quantitative assessment of tissue thermal conductivity. Such devices can also be implemented in ways that reveal the time-dynamic influence of blood flow and perfusion on these properties. Experimental and theoretical studies establish the underlying principles of operation, and define engineering guidelines for device design. Evaluation of subtle variations in skin temperature associated with mental activity, physical stimulation and vasoconstriction/dilation along with accurate determination of skin hydration through measurements of thermal conductivity represent some important operational examples.

Vasculopathy, inflammation, and blood flow in leg ulcers of patients with sickle cell anemia.

Chronic leg ulcers are frequent and debilitating complications of sickle cell anemia. Inadequate blood supply has been postulated to be an important factor in their occurrence and delayed healing. Little is known about their microcirculatory and histopathological changes. We evaluated the microcirculation of lower extremity ulcers with laser speckle contrast imaging and infrared thermography and obtained clinical and laboratory characteristics in 18 adults with sickle cell anemia and chronic leg ulcers. Skin biopsies were obtained in four subjects. Subjects had markers of severe disease, anemia, high degree of hemolysis, inflammation, and thrombophilia. The highest blood flow was present in the ulcer bed, progressively less in the immediate periwound area, and an unaffected control skin area in the same extremity. Microscopic examination showed evidence of venostasis, inflammation, and vasculopathy. Blood vessels were increased in number, had activated endothelium and evidence of thrombosis/recanalization. High blood flow may be due to chronic inflammation, cutaneous vasodilatation, venostasis, and in situ thrombosis. These changes in skin microcirculation are similar to chronic venous ulcers in the non-sickle cell disease (SCD) population, thus suggesting that leg ulcers may be another end-organ complication with endothelial dysfunction that appears in patients with SCD at a younger age and with higher frequency than in the general population.

Increased brain microvascular hemoglobin concentrations in children with cerebral malaria.

Brain swelling is associated with death from cerebral malaria, but it is unclear whether brain swelling is caused by cerebral edema or vascular congestion-two pathological conditions with distinct effects on tissue hemoglobin concentrations. We used near-infrared spectroscopy (NIRS) to noninvasively study cerebral microvascular hemoglobin concentrations in 46 Malawian children with cerebral malaria. Cerebral malaria was defined by the presence of the malaria parasite Plasmodium falciparum on a blood smear, a Blantyre coma score of 2 or less, and retinopathy. Children with uncomplicated malaria (n = 33) and healthy children (n = 29) were enrolled as comparators. Cerebral microvascular hemoglobin concentrations were higher among children with cerebral malaria compared with those with uncomplicated malaria [median (25th, 75th): 145.2 (95.2, 190.0) µM versus 82.9 (65.7, 105.4) µM, P = 0.008]. Cerebral microvascular hemoglobin concentrations correlated with brain swelling score determined by MRI (r = 0.37, P = 0.03). Fluctuations in cerebral microvascular hemoglobin concentrations over a 30-min time period were characterized using detrended fluctuation analysis (DFA). DFA determined self-similarity of the cerebral microvascular hemoglobin concentration signal to be lower among children with cerebral malaria compared with those with uncomplicated malaria [0.63 (0.54, 0.70) versus 0.91 (0.82, 0.94), P < 0.0001]. The lower self-similarity of the hemoglobin concentration signal in children with cerebral malaria suggested impaired regulation of cerebral blood flow. The elevated cerebral tissue hemoglobin concentration and its correlation with brain swelling suggested that excess blood volume, potentially due to vascular congestion, may contribute to brain swelling in cerebral malaria.

Infrared imaging of nitric oxide-mediated blood flow in human sickle cell disease.

Vascular dysfunction is an important pathophysiologic manifestation of sickle cell disease (SCD), a condition that increases risk of pulmonary hypertension and stroke. We hypothesized that infrared (IR) imaging would detect changes in cutaneous bloodflow reflective of vascular function. We performed IR imaging and conventional strain gauge plethysmography in twenty-five adults with SCD at baseline and during intra-arterial infusions of an endothelium-dependent vasodilator acetylcholine (ACh), an endothelium-independent vasodilator sodium nitroprusside (SNP), and a NOS inhibitor L-NMMA. Skin temperature measured by IR imaging increased in a dose-dependent manner to graded infusions of ACh (+1.1°C, p<0.0001) and SNP (+0.9°C, p<0.0001), and correlated with dose-dependent increases in forearm blood flow (ACh: +19.9 mL/min/100 mL, p<0.0001; r(s)=0.57, p=0.003; SNP: +8.6 mL/min/100 mL, p<0.0001; r=0.70, p=0.0002). Although IR measurement of skin temperature accurately reflected agonist-induced increases in blood flow, it was less sensitive to decreases in blood flow caused by NOS inhibition. Baseline forearm skin temperature measured by IR imaging correlated significantly with baseline forearm blood flow (31.8±0.2°C, 6.0±0.4 mL/min/100 mL; r=0.58, p=0.003), and appeared to represent a novel biomarker of vascular function. It predicted a blunted blood flow response to SNP (r=-0.61, p=0.002), and was independently associated with a marker of pulmonary artery pressure, as well as hemoglobin level, diastolic blood pressure, homocysteine, and cholesterol (R(2)=0.84, p<0.0001 for the model). IR imaging of agonist-stimulated cutaneous blood flow represents a less cumbersome alternative to plethysmography methodology. Measurement of baseline skin temperature by IR imaging may be a useful new marker of vascular risk in adults with SCD.

A Platform to Record Patient Events During Physiological Monitoring With Wearable Sensors: Proof-of-Concept Study.

BACKGROUND: Patient journals have been used as valuable resources in clinical studies. However, the full potential value of such journals can be undermined by inefficiencies and ambiguities associated with handwritten patient reports. The increasing number of mobile phones and mobile-based health care approaches presents an opportunity to improve communications from patients to clinicians and clinical researchers through the use of digital patient journals. OBJECTIVE: The objective of this project was to develop a smartphone-based platform that would enable patients to record events and symptoms on the same timeline as clinical data collected by wearable sensors. METHODS: This platform consists of two major components: a smartphone for patients to record their journals and wireless sensors for clinical data collection. The clinical data and patient records are then exported to a clinical researcher interface, and the data and journal are processed and combined into a single time-series graph for analysis. This paper gives a block diagram of the platform's principal components and compares its features to those of other methods but does not explicitly discuss the process of design or development of the system. RESULTS: As a proof of concept, body temperature data were obtained in a 4-hour span from a 22-year-old male, during which the subject simultaneously recorded relevant activities and events using the iPhone platform. After export to a clinical researcher's desktop, the digital records and temperature data were processed and fused into a single time-series graph. The events were filtered based on specific keywords to facilitate data analysis. CONCLUSIONS: We have developed a user-friendly patient journal platform, based on widely available smartphone technology, that gives clinicians and researchers a simple method to track and analyze patient activities and record the activities on a shared timeline with clinical data from wearable devices.

Assessment of critical renal ischemia with real-time infrared imaging.

BACKGROUND: Currently visual and tactile clues such as color, mottling, and tissue turgor are used in the operating room for subjective assessments of organ ischemia. Studies have demonstrated that infrared (IR) imaging is a reliable tool to identify perfusion of brain tumors and kidneys during human surgery. Intraoperative IR imaging has the potential for more objective real-time detection and quantitative assessment of organ viability including early ischemia. We hypothesize, by detecting variations of the IR signal, we can assess the degree to which renal surface temperature reflects underlying renal ischemia. To address this hypothesis, IR imaging-derived temperature fluctuations were evaluated during laparotomy in a porcine model (n = 15). These temperature profiles then underwent spectral (frequency) analysis to assess their relationship to well-described oscillations of the microcirculation. MATERIALS AND METHODS: An IR camera was positioned 30-60 cm above the exposed kidneys. Images (3-5 mum wavelength) were collected (1.0/s) at baseline, during warm renal ischemia, and during reperfusion. Dominant frequency (DF) of the tissue temperature fluctuations were determined by a Fourier transformation (spectral) analysis. RESULTS: IR images immediately showed which segments of the kidney were ischemic. DF at approximately 0.008 Hz that corresponds to blood flow oscillations was observed in thermal profiles. The oscillations were diminished or disappeared after 25 min of warm ischemia and were recovered with reperfusion in a time-dependent fashion. Oscillations were attenuated substantially in ischemic segments, but not in perfused segments of the kidney. CONCLUSIONS: The described oscillations can be measured noninvasively using IR imaging in the operating room, as represented by the DF, and may be an early marker of critical renal ischemia.

Evaluation of real-time infrared intraoperative cholangiography in a porcine model.

BACKGROUND: Intraoperative cholangiograms (IOCs) may increase cost, surgical time, and radiation exposure of staff and patients. The authors introduce the application of passive infrared imaging to intraoperative cholangiography as a feasible alternative to traditional fluoroscopic IOCs. METHODS: A porcine model was used in which the gallbladder, cystic duct, common bile duct (CBD), and duodenum were exposed and an 18-gauge angiocatheter was inserted into the cystic duct. Infrared emission was detected using a digital infrared camera positioned 30 to 60 cm above the abdomen. Infrared images were taken in real time (approximately 1/s) during infusion of room-temperature saline. A thermoplastic polymer stone then was inserted into the CBD. Once the artificial stone was placed, room-temperature saline was again injected. A standard single-shot renograffin IOC was obtained to confirm the obstruction. The experiment was concluded by creation of a lateral 2-mm CBD injury immediately proximal to the duodenum followed by infusion of room-temperature saline. RESULTS: Six pigs were used in this study. Baseline infrared imaging was able to capture a visible temperature decrease, outlining the lumen of the CBD. With injection of room-temperature saline, a decrease in temperature was visualized as a dark area representing flow from the CBD to the duodenum. After placement of the synthetic stone, real-time infrared images displayed slowing of the injected bolus by the obstruction. The obstruction was correlated with fluoroscopic IOCs. Finally, after partial transection of the CBD, the infrared camera visualized saline flowing from the site of injury out into the peritoneal cavity. CONCLUSIONS: The CBD anatomy, obstruction, and injury can be clearly visualized with an infrared camera. Intraoperative infrared imaging is an emerging method already being used in several surgical fields. Ultimately, the integration of infrared and laparoscopic technology will be necessary to make infrared technology important in laparoscopic cholecystectomy.

Rapid vs. delayed infrared responses after ischemia reveal recruitment of different vascular beds.

Continuous infrared imaging revealed transient changes in forearm temperature during arterial occlusion, reperfusion, and recovery in a healthy subject group. Processing the imaging data with the k-means algorithm further revealed reactive vascular sites in the skin with rapid or delayed temperature amplification. The observed temporal and spatial diversity of blood-flow-derived forearm temperature allow consideration of thermal-imaging guided placement of skin sensors to achieve enhanced sensitivity in monitoring of skin hemodynamics.

Epidermal devices for noninvasive, precise, and continuous mapping of macrovascular and microvascular blood flow.

Continuous monitoring of variations in blood flow is vital in assessing the status of microvascular and macrovascular beds for a wide range of clinical and research scenarios. Although a variety of techniques exist, most require complete immobilization of the subject, thereby limiting their utility to hospital or clinical settings. Those that can be rendered in wearable formats suffer from limited accuracy, motion artifacts, and other shortcomings that follow from an inability to achieve intimate, noninvasive mechanical linkage of sensors with the surface of the skin. We introduce an ultrathin, soft, skin-conforming sensor technology that offers advanced capabilities in continuous and precise blood flow mapping. Systematic work establishes a set of experimental procedures and theoretical models for quantitative measurements and guidelines in design and operation. Experimental studies on human subjects, including validation with measurements performed using state-of-the-art clinical techniques, demonstrate sensitive and accurate assessment of both macrovascular and microvascular flow under a range of physiological conditions. Refined operational modes eliminate long-term drifts and reduce power consumption, thereby providing steps toward the use of this technology for continuous monitoring during daily activities.

Intraoperative infrared imaging of brain tumors.

OBJECT: Although clinical imaging defines the anatomical relationship between a brain tumor and the surrounding brain and neurological deficits indicate the neurophysiological consequences of the tumor, the effect of a brain tumor on vascular physiology is less clear. METHODS: An infrared camera was used to measure the temperature of the cortical surface before, during, and after removal of a mass in 34 patients (primary brain tumor in 21 patients, brain metastases in 10 and falx meningioma, cavernous angioma, and radiation necrosis-astrocytosis in one patient each). To establish the magnitude of the effect on blood flow induced by the tumor, the images were compared with those from a group of six patients who underwent temporal lobectomy for epilepsy. In four cases a cerebral artery was temporarily occluded during the course of the surgery and infrared emissions from the cortex before and after occlusion were compared to establish the relationship of local temperature to regional blood flow. Discrete temperature gradients were associated with surgically verified lesions in all cases. Depending on the type of tumor, the cortex overlying the tumor was either colder or warmer than the surrounding cortex. Spatial reorganization of thermal gradients was observed after tumor resection. Temperature gradients of the cortex in patients with tumors exceeded those measured in the cortex of patients who underwent epilepsy surgery. CONCLUSIONS: Brain tumors induce changes in cerebral blood flow (CBF) in the cortex, which can be made visible by performing infrared imaging during cranial surgery. A reduction in CBF beyond the tumor margin improves after removal of the lesion.

Real-time detection of vascular occlusion and reperfusion of the brain during surgery by using infrared imaging.

OBJECT: Application of sensitive infrared imaging is ideally suited to observe blood vessels and blood flow in exposed organs, including the brain. Temporary vascular occlusion is an important part of neurosurgery, but the capacity to monitor the effects of these occlusions in real time is limited. In surgical procedures that require vascular manipulation, such as those involving aneurysms, arteriovenous malformations (AVMs), or tumors, the ability to visualize blood flow in vessels and their distribution beds would be beneficial. The authors recount their experience in the use of a sensitive (0.02 degrees C), high-resolution (up to 50 microm/pixel) infrared camera with a rapid shutter speed (up to 2 msec/frame) for localizing cortical function intraoperatively. They observed high-resolution images of cerebral arteries and veins. The authors hypothesized that infrared imaging of cerebral arteries, performed using a sensitive, high-resolution camera during surgery, would permit changes in arterial flow to be be seen immediately, thus providing real-time assessment of brain perfusion in the involved vascular territory. METHODS: Cynomolgus monkeys underwent extensive craniectomies, exposing the frontal, parietal, and temporal lobes. Temporary occlusions of the internal carotid artery and middle cerebral artery branches (30 events) were performed serially and were visualized with the aid of an infrared camera. Arteries and veins of the monkey brain were clearly visualized due to cooling of the exposed brain, which contrasted with blood within the vessels that remained at core temperature. Blood flow changes in vessels were seen immediately (< 1 second) in real time during occlusion and reopening of the vessels, regardless of the duration of the occlusion. Areas of decreased cortical blood flow rapidly cooled (-0.3 to 1.3 degrees C) and reheated in response to reperfusion. Rewarming occurred faster in arteries than in the cortex (for a 20-minute occlusion, the change in temperature per second was 2 x 10(-2) degrees C in the artery and 7 x 10(-3) degrees C in the brain). Collateral flow could be evaluated by intraoperative observations and data processing. CONCLUSIONS: Use of high-resolution, digital infrared imaging permits real-time visualization of arterial flow. It has the potential to provide the surgeon with a means to assess collateral flow during temporary vessel occlusion and to visualize directly the flow in parent arteries or persistent filling of an aneurysm after clipping. During surgery for AVMs, the technique may provide a new way to assess arterial inflow, venous outflow, results of embolization, collateral flow, steal, and normal perfusion pressure breakthrough.

Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance.

Resistance to chemotherapy is the primary cause of treatment failure in over 90% of cancer patients in the clinic. Research in nanotechnology-based therapeutic alternatives has helped provide innovative and promising strategies to overcome multidrug resistance (MDR). By targeting CD44-overexpressing MDR cancer cells, we have developed in a single-step a self-assembled, self-targetable, therapeutic semiconducting single-walled carbon nanotube (sSWCNT) drug delivery system that can deliver chemotherapeutic agents to both drug-sensitive OVCAR8 and resistant OVCAR8/ADR cancer cells. The novel nanoformula with a cholanic acid-derivatized hyaluronic acid (CAHA) biopolymer wrapped around a sSWCNT and loaded with doxorubicin (DOX), CAHA-sSWCNT-DOX, is much more effective in killing drug-resistant cancer cells compared to the free DOX and phospholipid PEG (PL-PEG)-modified sSWCNT formula, PEG-sSWCNT-DOX. The CAHA-sSWCNT-DOX affects the viscoelastic property more than free DOX and PL-PEG-sSWCNT-DOX, which in turn allows more drug molecules to be internalized. Intravenous injection of CAHA-sSWCNT-DOX (12 mg/kg DOX equivalent) followed by 808 nm laser irradiation (1 W/cm(2), 90 s) led to complete tumor eradication in a subcutaneous OVCAR8/ADR drug-resistant xenograft model, while free DOX alone failed to delay tumor growth. Our newly developed CAHA-sSWCNT-DOX nanoformula, which delivers therapeutics and acts as a sensitizer to influence drug uptake and induce apoptosis with minimal resistance factor, provides a novel effective means of counteracting the phenomenon of multidrug resistance.

Topical sodium nitrite for chronic leg ulcers in patients with sickle cell anaemia: a phase 1 dose-finding safety and tolerability trial.

BACKGROUND: Well-tolerated and effective treatments are needed for chronic leg ulcers in sickle cell anaemia. Topical sodium nitrite, a known nitric oxide donor, enhances blood flow in ulcers and has known bacteriostatic effects. We aimed to assess the safety, tolerability, and pharmacokinetics of topical sodium nitrite in patients with sickle cell disease and chronic leg ulcers. METHODS: We enrolled adult patients from an ambulatory clinic at the National Institutes of Health (Bethesda, MD, USA) with sickle cell anaemia with leg ulcers (with a surface area of 2.5-100 cm2) persisting for at least 4 weeks into a safety and tolerability phase 1 dose-escalation trial of topical sodium nitrite. Increasing concentrations of sodium nitrite cream were applied twice weekly for 4 weeks to one ulcer per patient at five dose levels (0.5%, 1%, 1.5%, 1.8%, and 2%). The primary endpoints were safety and tolerability, with secondary endpoints of pharmacokinetics, blood flow, and wound healing. Pain relief was analysed post hoc. Endpoints were analysed over time for the whole study population and according to dose level. This study is registered with ClinicalTrials.gov, number NCT01316796. FINDINGS: Between April 4, 2011, and March 19, 2013, we enrolled 18 adult patients with sickle cell anaemia and leg ulcers into our trial. We assigned three patients into each cohort, and each cohort was treated with a different concentration of sodium nitrite cream (cohort 1: 0.5%, cohort 2: 1.0%, cohort 3: 1.5%, and cohort 4: 2.0%). Patients were not enrolled into the next cohort dose until we were able to establish that no dose-limiting toxicities were observed. An additional six patients were enrolled to cohort 3a: 1.8%, after two patients in cohort 4 had asymptomatic drops in diastolic blood pressure. No grade 3-4 adverse events were observed, and there were no serious adverse events or dose-limiting side-effects. Pharmacokinetic analysis showed that systemic absorption of sodium nitrite was very low. Application of topical sodium nitrite was associated with a significant increase in peri-wound cutaneous blood flow measured by laser speckle contrast imaging (p=0.0002), corroborated by increased peri-wound skin temperature by infrared thermography (p=0.0119). We recorded a dose-dependent decrease in leg ulcer size (p=0.0012) and pain (p<0.0001). Ulcers healed completely in three patients who received the highest concentrations of topical sodium nitrite (the 1.8% and 2% cream). In our post-hoc analysis of pain, brief pain inventory scores improved in pain severity (p=0.0048) and pain interference (p=0.0013). INTERPRETATION: Our results indicate that topical sodium nitrite 2% cream is suitable for additional clinical trials in adults with sickle cell anaemia to promote healing of leg ulcers. FUNDING: National Heart, Lung and Blood Institute Division of Intramural Research (National Institutes of Health).

Mast cell dependent vascular changes associated with an acute response to cold immersion in primary contact urticaria.

BACKGROUND: While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation. OBJECTIVE: To characterize the microcirculatory events that follow mast cell degranulation. METHODOLOGY/PRINCIPAL FINDINGS: Perturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine. CONCLUSIONS/SIGNIFICANCE: Monitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention.

Physiological parameter monitoring from optical recordings with a mobile phone.

We show that a mobile phone can serve as an accurate monitor for several physiological variables, based on its ability to record and analyze the varying color signals of a fingertip placed in contact with its optical sensor. We confirm the accuracy of measurements of breathing rate, cardiac R-R intervals, and blood oxygen saturation, by comparisons to standard methods for making such measurements (respiration belts, ECGs, and pulse-oximeters, respectively). Measurement of respiratory rate uses a previously reported algorithm developed for use with a pulse-oximeter, based on amplitude and frequency modulation sequences within the light signal. We note that this technology can also be used with recently developed algorithms for detection of atrial fibrillation or blood loss.

Reconstruction of Thermographic Signals to Map Perforator Vessels in Humans.

Thermal representations on the surface of a human forearm of underlying perforator vessels have previously been mapped via recovery-enhanced infrared imaging, which is performed as skin blood flow recovers to baseline levels following cooling of the forearm. We noted that the same vessels could also be observed during reactive hyperaemia tests after complete 5-min occlusion of the forearm by an inflatable cuff. However, not all subjects showed vessels with acceptable contrast. Therefore, we applied a thermographic signal reconstruction algorithm to reactive hyperaemia testing, which substantially enhanced signal-to-noise ratios between perforator vessels and their surroundings, thereby enabling their mapping with higher accuracy and a shorter occlusion period.

Observing temperature fluctuations in humans using infrared imaging.

In this work we demonstrate that functional infrared imaging is capable of detecting low frequency temperature fluctuations in intact human skin and revealing spatial, temporal, spectral, and time-frequency based differences among three tissue classes: microvasculature, large sub-cutaneous veins, and the remaining surrounding tissue of the forearm. We found that large veins have stronger contractility in the range of 0.005-0.06 Hz compared to the other two tissue classes. Wavelet phase coherence and power spectrum correlation analysis show that microvasculature and skin areas without vessels visible by IR have high phase coherence in the lowest three frequency ranges (0.005-0.0095 Hz, 0.0095-0.02 Hz, and 0.02-0.06 Hz), whereas large veins oscillate independently.

Core body temperature in obesity.

BACKGROUND: A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity. OBJECTIVE: We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals. DESIGN: In study 1, nonobese [body mass index (BMI; in kg/m(2)) <30] and obese (BMI ≥30) adults swallowed wireless core temperature-sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18-25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for ≥48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis. RESULTS: Mean (±SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 ± 0.03°C compared with 36.89 ± 0.03°C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature ≈0.23°C greater than that of men (36.99 ± 0.03°C compared with 36.76 ± 0.03°C; P < 0.0001). CONCLUSIONS: Obesity is not generally associated with a reduced core body temperature. It may be necessary to study individuals with function-altering mutations in core temperature-regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500.

Skin surface temperature rhythms as potential circadian biomarkers for personalized chronotherapeutics in cancer patients.

Chronotherapeutics involve the administration of treatments according to circadian rhythms. Circadian timing of anti-cancer medications has been shown to improve treatment tolerability up to fivefold and double efficacy in experimental and clinical studies. However, the physiological and the molecular components of the circadian timing system (CTS), as well as gender, critically affect the success of a standardized chronotherapeutic schedule. In addition, a wrongly timed therapy or an excessive drug dose disrupts the CTS. Therefore, a non-invasive approach to accurately detect and monitor circadian rhythms is needed for a dynamic assessment of the CTS in order to personalize chronomodulated drug delivery schedule in cancer patients. Since core body temperature is a robust circadian biomarker, we recorded temperature at multiple locations on the skin of the upper chest and back of controls and cancer patients continuously. Variability in the circadian phase existed among patch locations in individual subjects over the course of 2-6 days, demonstrating the need to monitor multiple skin temperature locations to determine the precise circadian phase. Additionally, we observed that locations identified by infrared imaging as relatively cool had the largest 24 h temperature variations. Disruptions in skin temperature rhythms during treatment were found, pointing to the need to continually assess circadian timing and personalize chronotherapeutic schedules.