We estimate the velocity field of the blood flow in a human face from videos. Our approach first performs spatial preprocessing to improve the signal-to-noise ratio (SNR) and the computational efficiency. The discrete Fourier transform (DFT) and a temporal band-pass filter are then applied to extract the frequency corresponding to the subjects heart rate. We propose multiple kernel based k-NN classification for removing the noise positions from the resulting phase and amplitude maps. The 2D blood flow field is then estimated from the relative phase shift between the pixels. We evaluate our approach about segmentation as well as velocity field on real and synthetic face videos. Our method produces the recall and precision as well as a velocity field with an angular error and magnitude error on the average.

Studies show that vasomotor and sudomotor activity is compromised in individuals with Type 1 Diabetes (T1DM) which could lead to altered thermoregulatory function. However, recent work suggests that the impairments may only be evidenced beyond a certain level of heat stress. We therefore examined T1DM-related differences in heat loss responses of sweating and skin blood flow (SkBF) during exercise performed at progressive increases in the requirement for heat loss. Participants were matched for age, sex, body surface area and fitness cycled at fixed rates of metabolic heat production of 200, 250, and 300 W•m-2 of body surface area, each rate being performed sequentially for 30 min. Local sweat rate (LSR), sweat gland activation (SGA), and sweat gland output (SGO) were measured on the upper back, chest and forearm while SkBF (laser-Doppler) was measured on the forearm and upper back only. We found that despite a similar requirement for heat loss, LSR was lower in T1DM on the chest and forearm only, relative to Control and only different at the end of the second and third exercise periods. Differences in chest LSR were due to reduced SGA whereas the decreased forearm LSR was the result of a decrease in SGO. SkBF did not differ between groups. The reduction in the sweating response in the T1DM group was paralleled by a greater increase in core temperature. We show that T1DM impairs heat dissipation as evidenced by reductions in LSR and not SkBF. A compromised thermoregulatory response during and following physical exertion is of considerable concern due to the associated increased risk of post-exertion heat-related injury.

Aim The main aim of this study was to investigate if a combination of classic resistance training and blood flow restricted resistance exercise (BFRE) training would result in greater increases in quadriceps muscle growth compared with other strength training studies. The second aim was to investigate if there would be any difference in muscle hypertrophy between men and women after the training intervention.   Method Twenty untrained subjects (10 males and 10 female) were recruited to participate in a 10-week unilateral resistance training intervention. Sixteen subjects completed the training intervention. After two familiarization sessions subjects performed three sessions per week in leg press and leg extension, except for week 4 and 8 were subjects performed five BFRE training sessions Monday to Friday. All subjects performed a one repetition maximum test in leg press and leg extension pre and post the training intervention. Ultrasound screening was performed pre and post training intervention to measure muscle thickness in m. vastus lateralis (VL).   Results The 10-week intervention resulted in a significant increase of VL muscle thickness by 15,1 % ± 7,6 (p ≤ 0,01). Both men and women increased in VL muscle thickness, men (n=7) by 15,4 % ± 9,3 (p ≤ 0,01) and women (n=9) by 14,8 % ± 6,0 (p ≤ 0,01), with no difference between genders. Maximal strength increased for the entire group in the leg press by 59,1 % ± 27,4 (p ≤ 0,01) and in the leg extension by 19,8 % ± 13,1 (p ≤ 0,01). Men had an increase of 58,1 % ± 18,0 (p ≤ 0,01) and women with 60,3 % ± 32,8 (p ≤ 0,01) in the leg press. In the leg extension women and men increased their maximal strength by 23,3 % ± 7,4 (p ≤ 0,01) respectively 17,0 % ± 14,4 (p = 0,051).   Conclusions Our unique training protocol resulted in a superior increase in muscle growth in comparison with most other strength training studies. Our result can be converted to an increase of 17,3 % (0,25 % per day) in VL muscle CSA, which is much greater than the mean increase of 0,11 % per day reported in a large meta-analysis (Wernbom, Augustsson & Thomeé 2007).

The objective of this work is to develop a novel 3-D biological particulate dynamics framework to simulate blood flow in the micro circulation. This entails the amalgamation of concepts from various fields namely blood flow dynamics, solid mechanics, fluid-structure interaction and computational data structures. It is envisioned that this project will serve as a harbinger for implementing a multi-scale simulation model with applications in a vast array of situations from blood flows in heart valves to studying cancer metastasis. The primary motivation for this work stems from the need for establishing a simple, effective and holistic framework for performing blood flow simulations, taking into account the extremely 3-D nature of flow, the particle interactions and fluid structure interaction between blood and its constituent elements. Many current models to simulate blood cells rely on finite element methods which render large scale simulations extremely computationally intensive. The development of a framework for simulating blood flow is tied together with achieving a framework for performing an investigation of cancer metastasis. Cancer initially develops at a primary site and spreads through the body to secondary sites using the circulatory systems of the body - the blood circulatory system and the lymphatic system. It is known that all the cancer cells that enter into the circulation do not survive the harsh environment, though the exact cause of this is still undetermined. Moreover, the mechanical properties of cancer cells are not well documented and appropriate computational models require that experiments be conducted to determine the same. Thus the end goal of this work is to establish a system to analyze and simulate 3-D blood particulate dynamics, including cancer cells, from a holistic standpoint in order to understand more about the phenomenon of blood flow as a whole, and cancer metastasis in particular.

Introduction: Aging has been shown to diminish bone blood flow in rats and humans. The purpose of this study was to determine whether blood flow to regions of the femur perfused primarily through the principal nutrient artery (PNA) are diminished with aging and whether this putative reduction in flow is associated with impaired endothelium‐dependent vasodilation. Materials and Methods: Blood flow was measured in conscious young adult (4–6 mo old) and aged (24–26 mo old) male Fischer‐344 rats using radiolabeled microspheres. Endothelium‐dependent vasodilation of the PNA was assessed in vitro using acetylcholine (ACh), whereas the contribution of the NO synthase (NOS) and cyclooxygenase (COX) signaling pathways to endothelium‐dependent vasodilation was determined using the NOS and COX inhibitors L‐NAME and indomethacin, respectively. Results: Femoral blood flow in the aged rats was 21% and 28% lower in the proximal and distal metaphyses, respectively, and 45% lower in the diaphyseal marrow. Endothelium‐dependent vasodilation was reduced with old age (young: 83 ± 6% maximal relaxation; aged: 62 ± 5% maximal relaxation), whereas endothelium‐independent vasodilation (sodium nitroprusside) was unaffected by age. The reduction in endothelium‐dependent vasodilation was mediated through impairment of the NOS signaling pathway, which resulted in lower NO bioavailability (young: 168 ± 56 nM; aged: 50 ± 7 nM). Conclusions: These data show that reductions in metaphyseal bone and diaphyseal marrow perfusion with old age are associated with diminished endothelium‐dependent vasodilation through an impairment of the NOS mechanism. Such age‐related changes in bone perfusion and vascular NO signaling could impact clinical bone loss, increase risk of fracture, and impair fracture healing in the elderly.

Vascular disease is the leading cause of mortality and morbidity in the western world, and account for the 1 of every 3 death’s in the US, but a cure for vascular disease is yet to be realized. Hematopoietic stem progenitor cells (HSPCs) are mobilized from bone marrow and have the innate propensity to accelerate vascular repair by reendothelialization and revascularization of ischemic areas. The vasoreparative ability of HSPCs is largely due to their capacity to home to the areas of hypoxia and their sensitivity to hypoxia plays a critical role in the vasoreparative functions of these cells. The discovery of vasoreparative potential of HSPCs resulted in a breakthrough approach of cell-based therapies for the treatment of ischemic vascular diseases. However, success of this approach is essentially dependent on the number of cells that could be collected from an individual. Therefore, novel mechanism-based strategies are needed to enhance the outcomes of autologous cell-based therapies in poor mobilizers and older adults. Recent evidence of a potential role of the vasoprotective axis of the renin angiotensin system (RAS) in HSPCs functions offers a breakthrough. Angiotensin-(1-7), the primary mediator of the protective functions which acts on Mas receptor (MasR), is generated by angiotensin converting enzyme-2 (ACE2). In this study, we tested the effects of hypoxia on stimulation of vasoreparative potential of HSPCs and in upregulation of ACE2 and MasR. Importantly, we delineated the molecular mechanism of hypoxic exposure in regulation of ACE2 and MasR in a HIF1α- dependent manner and hypoxic exposure induced shedding of the membrane bound ACE2 in HSPCs. We used luciferase, a reporter assay, cell-based assays, gene/protein expression studies and pharmacological strategies in human and mouse HSPCs to test our hypotheses. To verify the biological significance of hypoxia, we performed in vivo studies in mice and humans, which recapitulated the in vitro observations on vascular protective axis of RAS in HSPCs. Collectively, these studies provided mechanistic insights into hypoxic regulation of vascular protective axis of RAS in HSPCs and also provided compelling evidence for the clinical use of hypoxia as a promising approach for enhancing the vasoreparative outcomes of cell-based therapies. / American Heart Association grant, 13SDG16960025 / National Institutes of Health, National institute of Aging (NIA), 1R01AG056881

Cette thèse porte sur l’étude de la séquence d’imagerie IRM IVIM (« Intravoxel incoherent motion »). Cette séquence permet l’étude des microvaisseaux sanguins tels que les capillaires, artérioles et veinules. Pour être sensible seulement aux groupes de spins non statiques dans les tissus, des gradients de diffusion sont ajoutés avant et après l’impulsion 180° d’une séquence d’écho de spin. La composante du signal correspondant aux spins qui diffusent dans le tissu peut être séparée de celle des spins en mouvement dans les vaisseaux sanguins qui est appelée signal IVIM. Ces deux composantes sont pondérées par f IVIM qui représente la fraction volumique du sang à l’intérieur du tissu. Le signal IVIM est en général modélisé par une fonction mono-exponentielle (ME) caractérisée par un coefficient de pseudo-diffusion D*. Nous proposons un modèle IVIM bi-exponentiel formé d’une composante lente caractérisée F slow et D* slow qui correspondrait aux capillaires comme dans le modèle ME, et d’une composante rapide caractérisée par F fast et D* fast qui correspondrait à des vaisseaux plus gros comme des artérioles et veinules. Ce modèle a été validé expérimentalement et des informations supplémentaires ont été obtenues en comparant les signaux expérimentaux avec un dictionnaire de signaux IVIM simulés numériquement. L’influence de la séquence d’impulsions, du temps de répétition et du temps d’encodage de diffusion a également été étudiée. Enfin, la séquence IVIM a été appliquée à l’étude d’un modèle animal de la maladie d’Alzheimer. / This PhD thesis is centered on the study of the IVIM (“Intravoxel Incoherent Motion”) MRI sequence. This sequence allows for the study of the blood microvasculature such as the capillaries, arterioles and venules. To be sensitive only to moving groups of spins, diffusion gradients are added before and after the 180° pulse of a spin echo (SE) sequence. The signal component corresponding to spins diffusing in the tissue can be separated from the one related to spins travelling in the blood vessels which is called the IVIM signal. These two components are weighted by f IVIM which represents the volume fraction of blood inside the tissue. The IVIM signal is usually modelled by a mono-exponential (ME) function and characterized by a pseudo-diffusion coefficient, D*. We propose instead a bi-exponential IVIM model consisting of a slow pool, characterized by F slow and D* slow corresponding to the capillaries as in the ME model, and a fast pool, characterized by F fast and D* fast, related to larger vessels such as medium-size arterioles and venules. This model was validated experimentally and more information was retrieved by comparing the experimental signals to a dictionary of simulated IVIM signals. The influence of the pulse sequence, the repetition time and the diffusion encoding time was also studied. Finally, the IVIM sequence was applied to the study of an animal model of Alzheimer’s disease.

This thesis sought to evaluate whether the increased risk of heat-related illness observed in black-African descendants stems from impairements in local- and whole-body heat loss responses in this ethnic group. To evaluate this, in separate studies local- (study 1) and whole–body (study 2) heat loss responses were compared in young men (18-30 y) of black-African (n=21) and Caucasian (n=21) descent, matched for physical characteristics and fitness and born and raised in the same temperate environment. In study 1, we compared nitric oxide-dependent skin blood flow and sweating responses in young men of black-African (n=10) and Caucasian (n=10) descent during rest, exercise, and recovery in the heat. Both groups rested for 10-min, and then performed 50-min of moderate-intensity exercise at 200 W/m2, followed by 30-min of recovery in hot-dry heat (35°C, 20% RH). Local cutaneous vascular conductance (CVC%max) and sweat rate (SR) were measured at two forearm skin sites treated with a) lactated-Ringer (Control), or b) 10 mM NG-nitro-L-arginine methyl ester (L‐NAME, NO synthase-inhibitor). L-NAME significantly reduced CVC%max throughout rest, exercise, and recovery in both groups (both p<0.001). However, there were no significant main effects for the NO contribution to CVC%max between groups (all p>0.500). L-NAME significantly reduced local SR in both groups (both p<0.050). The NO contribution to SR was similar between groups such that L-NAME reduced SR relative to control at 40 and 50 min into exercise (both p<0.050). In study 2, we assessed whole-body total heat loss (evaporative + dry heat exchange) in black-African (n=11) and Caucasian (n=11) men using direct calorimetry. Participants performed three, 30-min bouts of semi-recumbent cycling at fixed metabolic heat productions (and therefore matched heat loss requirements between groups) of 200 (light), 250 (moderate), and 300 W/m2 (vigorous), each followed by 15-min recovery, in dry heat (40°C, ~13% relative humidity). Across all exercise bouts, dry (p=0.435) and evaporative (p=0.600) heat exchange did not differ significantly between groups. As such, total heat loss during light, moderate and vigorous exercise was similar between groups (p=0.777), averaging ((mean (SD)); 177 (10), 217 (13) and 244 (20) W/m2 in men of black-African descent, and 172 (13), 212 (17) and 244 (17) W/m2 in Caucasian men. Accordingly, body heat storage across all exercise bouts (summation of metabolic heat production and total heat loss) was also similar between the black-African (568 (142) kJ) and Caucasian groups (623 (124) kJ; p=0.356). This thesis demonstrates that ethnicity does not influence NO-dependent cutaneous vasodilation and sweating in healthy, young black-African descent and Caucasian men during exercise in the heat. Furthermore, we extend upon these observations by showing no differences in whole-body dry and evaporative heat exchange and therefore body heat storage.

PURPOSE: This study aims to quantify the retinal vascular blood flow in eyes affected by unilateral central retinal vein occlusions (CRVO) or branch retinal vein occlusions (BRVO). We created and explored a new, unitless metric for the severity of these diseases: relative blood flow (RBF). We then contextualized RBF in terms of patient demographics, ocular presentation and other systemic conditions, as well as explored its efficacy as a predictor of future outcomes. METHODS: Data was collected from 20 control subjects and 32 patients with clinically diagnosed retinal vein occlusions (15 CRVO and 17 BRVO). Laser speckle flowgraphy was then used to quantify retinal vascular blood flow in terms of mean blur rate, a metric shown to be highly heterogeneous between patients but fairly consistent in intra-patient repeated measurements over time. After confirming this and establishing a strong correlation between a healthy patient’s two eyes, we used an RVO patient’s fellow eye as a nondiseased expectation and presented relative blood flow as the ratio between their diseased and healthy eye. We then correlated this data with demographic variables and disease characteristics from patients’ medical history. RESULTS: We found an average blood flow decrease of 26% in CRVO eyes relative to healthy eyes in the same patients and an average decrease of 7% in BRVO eyes. In CRVO, duration of occlusion, central macular thickness, intraocular pressure, diabetes, previous laser and injection treatments, and an injection within three months after blood flow measurement were significantly associated with relative blood flow. In BRVO, no demographic variables or disease characteristics were significantly associated with relative blood flow. CONCLUSIONS: Relative blood flow represents a promising new, consistent and informative metric for quantifying the severity of unilateral retinal vein occlusions. With both descriptive and predictive properties in eyes with CRVO, future work should explore its great potential.

With high energy consumption and a low capacity for energy storage, the brain is highly dependent on a continuous supply of oxygen and nutrients from the bloodstream. Ischemic stroke, caused by the occlusion of a cerebral blood vessel, compromises cerebral blood flow (CBF), resulting in detrimental effects on brain homeostasis, vascular function, and neuronal health. Sex differences in ischemic stroke are known, with women having lower rates of stroke due to a protective role of estrogens on vascular health, and more severe strokes following reduced estrogen production after menopause. Rho-associated protein kinase (ROCK), an important regulator of vascular tone, also regulates vascular function in a sex-specific manner, and its deletion is neuroprotective following ischemic stroke. The current study explores the overlapping roles of ROCK and endogenous hormone influence on the acute CBF response to a photothrombotic (PT) model of ischemic stroke in mice. CBF was measured following stroke in the somatosensory cortex in mice with a heterozygous deletion of the ROCK2 isoform (ROCK2+/-) and in wild-type (WT) littermates. To remove endogenous hormones, male mice were gonadectomized (Gdx) and female mice were ovariectomized (Ovx), and control animals received a sham surgery (“intact”) prior to stroke induction. Intact WT males showed a delayed CBF drop compared to intact WT females, where peak drop in CBF wasn’t observed until 48 hours following stroke. Gonadectomy in males did not alter this response, however ovariectomy in females produced a “male-like” response. ROCK2+/- males also showed such phenotypic response, and Gdx did not alter this response, suggesting ROCK2 deletion or endogenous male hormones do not alter CBF response in males in this stroke model. Alternatively, intact ROCK2+/- females showed a striking difference in CBF values compared to intact WT females, where they displayed higher CBF values immediately post-stroke and also showed a peak drop in CBF at 48 hours post-stroke. Ovx did not change the CBF response in ROCK2+/- females. Overall, there is a marked difference between males and females in their acute CBF responses to PT stroke, which appears to be mediated by endogenous female sex hormones and ROCK2. All groups except for intact WT females show a delayed drop in CBF values, reaching a maximal drop in CBF at 48 hours following stroke induction. This may be due to hyperreactivity of female platelets and upregulation of RhoA/ROCK signaling in female platelets. Further research is required to confirm this speculation. This study reveals important sex-differences and the involvement of ROCK2 in acute CBF responses to PT stroke in mice.