Les nouvelles gamma-caméras à semi-conducteurs utilisant des détecteurs au CZT sont dédiées aux explorations cardiaques. Leurs sensibilité, résolution spatiale et en énergie nettement améliorées comparativement aux gamma-caméras conventionnelles sont une révolution en médecine nucléaire. Ces gamma-caméras utilisent de nouvelles géométries d’acquisition, de nouveaux algorithmes de reconstruction, et ouvrent de nouvelles perspectives dans les études simultanées en double-isotope de l’123I et du 99mTc, dont les pics énergétiques sont proches.Nous avons étudié l’impact de l’amélioration de la résolution en énergie en comparant deux modèles de gamma-caméras à détecteurs semi-conducteurs aux gamma-caméras conventionnelles. A l’aide d’études sur fantômes anthropomorphes et chez des patients porteurs d’insuffisance cardiaque, notre travail s’est concentré sur les acquisitions scintigraphiques (i) de la fonction ventriculaire gauche (99mTc) en présence d’123I, (ii) de la perfusion myocardique (99mTc) en présence d’123I (innervation), et (iii) du rapport cardiomédiastinal de la fixation d’123I- métaiodobenzylguanidine (123I-MIBG) lors d’acquisitions double-isotope (123I-MIBG/99mTc- tétrofosmine) chez les patients souffrant d’insuffisance cardiaque.Nos résultats montrent que la meilleure résolution en énergie des gamma-caméras CZT permet en étude double-isotope (i) une évaluation de la FEVG et du mouvement régional dans les différentes fenêtres d'énergie (123I ou 99mTc) et les types d'acquisition (simple- vs double-isotope), (ii) une évaluation simultanée et combinée de la perfusion (99mTc) et de l’innervation (123I) du myocarde, et (iii) l’évaluation du rapport cardiomédiastinal de la fixation d’123I-MIBG. Chacune de ces trois parties a fait l’objet d’une publication. / New dedicated-cardiac cameras using CZT detectors have dramatically transformed the routine of myocardial perfusion imaging. With a better count detection sensitivity, an improved spatial and energy resolution, they potentially enable combined assessment of myocardial innervation (123I) and perfusion (99mTc) within a single imaging session. These cameras images with different sharpness and contrast-to-noise ratios.Using two CZT cameras with anthropomorphic phantom, and clinical studies in heart failure patients, our work focused on (i) the left ventricular function assessment within the 99mTc window in presence of 123I, (ii) the evaluation of regional myocardial innervation (123I) and perfusion (99mTc) match and mismatch with single- (separate 123I and 99mTc acquisition) and simultaneous dual-isotope acquisitions, and (iii) the late heart-to-mediastinal ratio (HMR) of 123I-MIBG uptake determined using dual-isotope CZT acquisition with that determined using conventional planar imaging in patients with heart failure.Our results found no impact of the acquisition mode (single vs dual) or the type of CZT camera on 123I and 99mTc defect size and mismatch, LVEF, and HMR of 123I-MIBG uptake.This work provides a new step toward simultaneous dual-isotope acquisition for combined innervation, perfusion and ventricular function assessment.

The spleen is an important site for central regulation of immune function by noradrenergic sympathetic nerves, but little is known about this major region of neuroimmune communication in humans. Experimental studies using animal models have established that sympathetic innervation of the spleen is essential for cholinergic anti-inflammatory responses evoked by vagal nerve stimulation, and clinical studies are evaluating this approach for treating inflammatory diseases. Most data on sympathetic nerves in spleen derive from rodent studies, and this work has established that remodeling of sympathetic innervation can occur during inflammation. However, little is known about the effects of sepsis on spleen innervation. Our primary goals were to (i) localize noradrenergic nerves in human spleen by immunohistochemistry for tyrosine hydroxylase (TH), a specific noradrenergic marker, (ii) determine if nerves occur in close apposition to leukocytes, and (iii) determine if splenic sympathetic innervation is altered in patients who died from end stage sepsis. Staining for vesicular acetylcholine transporter (VAChT) was done to screen for cholinergic nerves. Archived paraffin tissue blocks were used. Control samples were obtained from trauma patients or patients who died after hemorrhagic stroke. TH + nerves were associated with arteries and arterioles in all control spleens, occurring in bundles or as nerve fibers. Individual TH + nerve fibers entered the perivascular region where some appeared in close apposition to leukocytes. In marked contrast, spleens from half of the septic patients lacked TH + nerves fibers and the average abundance of TH + nerves for the septic group was only 16% of that for the control group (control: 0.272 ± 0.060% area, n = 6; sepsis: 0.043 ± 0.026% area, n = 8; P < 0.005). All spleens lacked cholinergic innervation. Our results provide definitive evidence for the distribution of noradrenergic nerves in normal human spleen and the first evidence for direct sympathetic innervation of leukocytes in human spleen. We also provide the first evidence for marked loss of noradrenergic nerves in patients who died from sepsis. Such nerve loss could impair neuroimmunomodulation and may not be limited to the spleen.

Very little is known about the development of cardiac parasympathetic ganglia and cholinergic innervation of the mouse heart. Accordingly, we evaluated the growth of cholinergic neurons and nerve fibers in mouse hearts from embryonic day 18.5 (E18.5) through postnatal day 21(P21). Cholinergic perikarya and varicose nerve fibers were identified in paraffin sections immunostained for the vesicular acetylcholine transporter (VAChT). Satellite cells and Schwann cells in adjacent sections were identified by immunostaining for S100β calcium binding protein (S100) and brain-fatty acid binding protein (B-FABP). We found that cardiac ganglia had formed in close association to the atria and cholinergic innervation of the atrioventricular junction had already begun by E18.5. However, most cholinergic innervation of the heart, including the sinoatrial node, developed postnatally (P0.5-P21) along with a doubling of the cross-sectional area of cholinergic perikarya. Satellite cells were present throughout neonatal cardiac ganglia and expressed primarily B-FABP. As they became more mature at P21, satellite cells stained strongly for both B-FABP and S100. Satellite cells appeared to surround most cardiac parasympathetic neurons, even in neonatal hearts. Mature Schwann cells, identified by morphology and strong staining for S100, were already present at E18.5 in atrial regions that receive cholinergic innervation at later developmental times. The abundance and distribution of S100-positive Schwann cells increased postnatally along with nerve density. While S100 staining of cardiac Schwann cells was maintained in P21 and older mice, Schwann cells did not show B-FABP staining at these times. Parallel development of satellite cells and cholinergic perikarya in the cardiac ganglia and the increase in abundance of Schwann cells and varicose cholinergic nerve fibers in the atria suggest that neuronal-glial interactions could be important for development of the parasympathetic nervous system in the heart.

Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

Cat hair receptors were studied to determine whether they could be distinguished by the following receptive field characteristics: thickness of innervated guard hairs, distance between innervated follicles and receptive field size. Initially the receptors were classified as G1, GI, G2 or D on the basis of their velocity requirements for excitation, their degree of linear directionality, their vibrational sensitivity, and whether they were activated by movement of down hairs. It was found that the thickest guard hairs on the posterior aspect of a cat's hindleg were usually 4-5 times thicker than the thinnest guard hairs from the same area and that G1, GI and G2 neurons innervated the full range of guard hair thicknesses available. Although there was a tendency for thicker guard hairs to be more heavily innervated, none of the neurons studied innervated thick guard hairs exclusively. While movement of the down hair and most guard hairs within D-mechanoreceptive fields easily evoked activity, a few guard hairs were regularly found for which mechanical displacement did not elicit a discharge even though they were well within the receptive field. Receptive field sizes and nearest neighbor distances between innervated follicles were smaller for D than for G1, GI and G2 receptors and greater for G1 than GI and G2 receptors.

Spinal ligaments may be a significant source of chronic back pain, yet they are often disregarded by the clinical community due to a lack of information with regards to their material response, and innervation characteristics. The purpose of this dissertation was to characterize the material response of spinal ligaments and to review their innervation characteristics. Review of relevant literature revealed that all of the major spinal ligaments are innervated. They cause painful sensations when irritated and provide reflexive control of the deep spinal musculature. As such, including the neurologic implications of iatrogenic ligament damage in the evaluation of surgical procedures aimed at relieving back pain will likely result in more effective long-term solutions. The material response of spinal ligaments has not previously been fully quantified due to limitations associated with standard soft tissue testing techniques. The present work presents and validates a novel testing methodology capable of overcoming these limitations. In particular, the anisotropic, inhomogeneous material constitutive properties of the human supraspinous ligament are quantified and methods for determining the response of the other spinal ligaments are presented. In addition, a method for determining the anisotropic, inhomogeneous pre-strain distribution of the spinal ligaments is presented. The multi-axial pre-strain distributions of the human anterior longitudinal ligament, ligamentum flavum and supraspinous ligament were determined using this methodology. Results from this work clearly demonstrate that spinal ligaments are not uniaxial structures, and that finite element models which account for pre-strain and incorporate ligament’s complex material properties may provide increased fidelity to the in vivo condition.

The sympathetic (SNS) and parasympathetic (PSNS) branches of the autonomic nervous system (ANS) innervate the heart, exerting excitatory and inhibitory influences (respectively) over cardiac functions (heart rate, AV conduction velocity, and contractility). However, the distribution and structure of SNS and PSNS innervation has not yet been well studied. Detailed characterization of the distributional organization and structural morphology of the SNS and PSNS in normal states is essential to the study of pathological autonomic remodeling. The present study utilized double immunohistochemical labeling techniques to examine tyrosine hydroxylase (TH) immunoreactive (IR) SNS and vesicular acetylcholine transporter (VAChT) IR PSNS axons and terminal structures in whole-mount atria of C57BL/6 mice. We found that: (1) The atria contain a dense network of ANS axons. TH-IR, VAChT-IR, and dual cholinergic/dopaminergic TH+VAChT-IR axons travel together in bundles on the epicardium before branching into differentiated terminal structures. (2) Parallel TH-IR and VAChT-IR axons often diverge from epicardial bundles and travel in parallel (less than 1μm apart) before forming terminal structures in the epicardium and myocardium. Such parallel SNS/PSNS axons interdigitize and have large alternating varicosities along their length adjacent to one other, suggesting possible antagonistic communication between both branches of the ANS at the prejunctional level. (3) Intrinsic cardiac ganglia (ICG) are targets for extrinsic sympathetic nerves which travel through ICG without forming large synaptic varicosities around cardiac principal neurons (PNs). (4) Small intensely fluorescent (SIF) cells (presumably chemoreceptors and/or interneurons) exist near SNS bundles, inside ICG, and in the epicardium unaccompanied by ganglia and nerve bundles. (5) The subpopulation of TH+VAChT-IR PNs within ICG form loose terminals in the atria and do not project to other PNs. (6) Both TH-IR and VAChT-IR axons innervate atrial vasculature. (7) TH-IR axons innervate fat pads adjacent to the heart. (8) SNS/PSNS parallelism is not exclusive to the atria. Similar structures exist in the esophagus, right ventricle, and small intestine. This study provides a novel and overall view of the innervation and interaction of the SNS and PSNS in the atria. This will underlie a foundation for future physiological, pharmacological, and anatomical studies of SNS/PSNS innervation, interaction, and remodeling in pathological states (such as aging, intermittent hypoxia and diabetes).

The purpose of this literature review was to identify any adaptations that could be made to the rehabilitation process for Traumatic Transfemoral Amputees. Traumatic Transfemoral Amputation is particularly debilitating with the amputees encountering many obstacles throughout the rehabilitation process. These obstacles can prevent the return to pre-morbid functioning. With an ever-increasing number of amputees within the United States, it is imperative the rehabilitation process be addressed. This literature review addresses possible adjustments in the initial stages of rehabilitation examining the post-operative, pre-prosthetic, and prosthetic rehabilitation stage to enhance the physical functioning for the amputee. This comprehensive literature review encompassing 63 academic and medical journals analyzes the research literature regarding each of the three stages of the post-operative procedure. The literature review synthesizes the research findings to see how procedures may be adapted to reduce the risk of further co-morbidities such as loss of bone mineral density and disuse atrophy. Loss of bone mineral density and disuse atrophy are the major contributing factors to the amputees decreased mobility. Reducing this loss can be addressed within the initial post-operative, pre-prosthetic, and prosthetic rehabilitation stages. Further research is required to examine the efficacy of these alterations in relation to this specific population.

The purpose of this study was to use retrograde tracing techniques to examine hepatic neuroanatomy in the rat model, with special emphasis upon the identification of previously undiscovered intrahepatic parasympathetic ganglia. Retrograde analysis was performed using Fluoro-Gold (FG) tracer injections of both male and female Sprague-Dawley rats. To accurately examine the neural connectivity of both the vasculature and the parenchyma, the FG-labelled livers were divided into two groups. In the first, vessel trees were extracted via dissection and whole-mounted for bright field and confocal visualization. Left lateral lobes taken from the male and female liver that constituted the second group were sectioned, and slices from various layers of tissue were fixed to slides and visualized. The results indicated the presence of several large, fluorescent structures bearing a strong resemblance to parasympathetic ganglia. However, the images were not detailed enough to properly differentiate true ganglia from similar paraganglia. Regardless, the importance of this experiment lies in its attempt to revisit an understudied field in neuroscience, and the findings of this study could potentially provide a starting point for further inquiry.

No description available.