Biometric and physiological factors in human ocular perfusion

By addressing the vascular features that characterise myopia, this thesis aims to provide an understanding of the early structural changes associated with human myopia and the progression to co-morbidity with age. This thesis addresses three main areas of study: 1. Ocular perfusion features and autoregulatory mechanisms in human myopia; 2. Choroidal thickness at the macular area of myopic eyes; 3. Effect of chronic smoking on the ocular haemodynamics and autoregulation. This thesis demonstrated a reduced resting ocular pulse amplitude and retrobulbar blood flow in human myopia, associated with an apparent oversensitivity to the vasodilatory effects of hypercapnia, which may be due to anatomical differences in the volume of the vessel beds. In young smokers, normal resting state vascular characteristics were present; however there also appeared to be increased reactivity to hypercapnia, possibly due to relative chronic hypoxia. The systemic circulation in myopes and smokers over-reacted similarly to hypercapnia suggesting that physiologic differences are not confined to the eye. Age also showed a negative effect on autoregulatory capacity in otherwise normal eyes. Collectively, these findings suggest that myopes and smokers require greater autoregulatory capacity to maintain appropriate oxygenation of retinal tissue, and since the capacity for such regulation reduces with age, these groups are at greater risk of insufficient autoregulation and relative hypoxia with age.

Identification of a time-dependent bio-heat blood perfusion coefficient

In the paper the identification of the time-dependent blood perfusion coefficient is formulated as an inverse problem. The bio-heat conduction problem is transformed into the classical heat conduction problem. Then the transformed inverse problem is solved using the method of fundamental solutions together with the Tikhonov regularization. Some numerical results are presented in order to demonstrate the accuracy and the stability of the proposed meshless numerical algorithm.

The blood perfusion and NADH/FAD content combined analysis in patients with diabetes foot

Skin blood microcirculation and the metabolism activity of tissue were examined on the patients with type 2 diabetes. Laser Doppler flowmetry (LDF) with 1064 nm laser light source and fluorescence spectroscopy (FS) with excitation light of 365 nm and 450 nm have been used to monitor the blood perfusion and the content of coenzymes NADH and FAD. Concluding, the proposed combined LDF and tissue FS approach allows to identify the significant violations in the blood microcirculation and metabolic activity for type 2 diabetes patients.

Altered hippocampal function in major depression despite intact structure and resting perfusion

A.F. is supported by Research Capability Funding from the Northumberland-Tyne-and-Wear NHS Foundation Trust awarded to R.H.M.-W.

Computed Tomography Perfusion Can Guide Endovascular Therapy in Bilateral Carotid Artery Dissection

Carotid artery dissection (CAD) is a major cause of stroke in those under age 45, accounting for around 20% of ischaemic events[1,2]. In the absence of known connective tissue disorders, most dissections are traumatic[2]. First-line management is comprised of antiplatelet or anticoagulation therapy, but many traumatic dissections progress despite this and carry the risk of long-term complications from embolism or stenosis[3]. We report a case of traumatic bilateral carotid dissection leading to progressive neurological symptoms and hypoperfusion on computed tomography perfusion (CTP), despite escalation in anticoagulation, which led to emergency carotid stenting.

Cerebral misery perfusion diagnosed using hypercapnic blood-oxygenation-level-dependent contrast functional magnetic resonance imaging: a case report

Introduction Cerebral misery perfusion represents a failure of cerebral autoregulation. It is animportant differential diagnosis in post-stroke patients presenting with collapses in the presence of haemodynamically significant cerebrovascular stenosis. This is particularly the case when cortical or internal watershed infarcts are present. When this condition occurs, further investigation should be done immediately. Case presentation A 50-year-old Caucasian man presented with a stroke secondary to complete occlusion of his left internal carotid artery. He went on to suffer recurrent seizures. Neuroimaging demonstrated numerous new watershed-territory cerebral infarcts. No source of arterial thromboembolism was demonstrable. Hypercapnic blood-oxygenation-level-dependent-contrast functional magnetic resonance imaging was used to measure his cerebrovascular reserve capacity. The findings were suggestive of cerebral misery perfusion. Conclusions Blood-oxygenation-level-dependent-contrast functional magnetic resonance imaging allows the inference of cerebral misery perfusion. This procedure is cheaper and more readily available than positron emission tomography imaging, which is the current gold standard diagnostic test. The most evaluated treatment for cerebral misery perfusion is extracranial-intracranial bypass. Although previous trials of this have been unfavourable, the results of new studies involving extracranial-intracranial bypass in high-risk patients identified during cerebral perfusion imaging are awaited. Cerebral misery perfusion is an important and under-recognized condition in which emerging imaging and treatment modalities present the possibility of practical and evidence-based management in the near future. Physicians should thus be aware of this disorder and of recent developments in diagnostic tests that allow its detection.

New methodologies in CT perfusion and MRI analysis to develop cancer imaging biomarkers

Quantitative imaging in oncology aims at developing imaging biomarkers for diagnosis and prediction of cancer aggressiveness and therapy response before any morphological change become visible. This Thesis exploits Computed Tomography perfusion (CTp) and multiparametric Magnetic Resonance Imaging (mpMRI) for investigating diverse cancer features on different organs. I developed a voxel-based image analysis methodology in CTp and extended its use to mpMRI, for performing precise and accurate analyses at single-voxel level. This is expected to improve reproducibility of measurements and cancer mechanisms’ comprehension and clinical interpretability. CTp has not entered the clinical routine yet, although its usefulness in the monitoring of cancer angiogenesis, due to different perfusion computing methods yielding unreproducible results. Instead, machine learning applications in mpMRI, useful to detect imaging features representative of cancer heterogeneity, are mostly limited to clinical research, because of results’ variability and difficult interpretability, which make clinicians not confident in clinical applications. In hepatic CTp, I investigated whether, and under what conditions, two widely adopted perfusion methods, Maximum Slope (MS) and Deconvolution (DV), could yield reproducible parameters. To this end, I developed signal processing methods to model the first pass kinetics and remove any numerical cause hampering the reproducibility. In mpMRI, I proposed a new approach to extract local first-order features, aiming at preserving spatial reference and making their interpretation easier. In CTp, I found out the cause of MS and DV non-reproducibility: MS and DV represent two different states of the system. Transport delays invalidate MS assumptions and, by correcting MS formulation, I have obtained the voxel-based equivalence of the two methods. In mpMRI, the developed predictive models allowed (i) detecting rectal cancers responding to neoadjuvant chemoradiation showing, at pre-therapy, sparse coarse subregions with altered density, and (ii) predicting clinically significant prostate cancers stemming from the disproportion between high- and low- diffusivity gland components.

Effetto dell' ormone tiroideo (T3) durante ex vivo lung perfusion (EVLP) sul polmone di ratto: valutazione dell'azione protettiva nel danno da ischemia riperfusione.

La perfusione polmonare extracorporea (EVLP) è una tecnica utilizzata dal 2010 per valutare e migliorare la qualità dell'organo da trapiantare e il danno da ischemia-ripefusione (IRI). Tale perfusione utilizza la soluzione di Steen, la cui composizione è solo parzialmente nota. Lo scopo è quello di identificare gli effetti di T3 su IRI polmonare ex vivo, in un modello di ratto di donatore a cuore non battente. Animali (40) randomizzati in otto gruppi e il protocollo EVLP sono stati standardizzati nel nostro centro. Sono state valutate la funzione polmonare, PEEP, la resistenza vascolare polmonare totale a 45, 60, 120 e 180 minuti di EVLP per eseguire analisi di gas, dosaggio del mediatore di infiammazione, mitocondriale libero DNA, freeT3 e freeT4. Alla fine dei campioni di tessuto polmonare sono stati congelati dal dosaggio ATP, espressione genica, DNA mitocondriale, T3. Non date le concentrazioni del produttore, abbiamo analizzato gli acidi grassi liberi, vitamine, ormoni e composizione della soluzione Steen. Risultati La soluzione di steen contiene albumina umana x2 nel siero umano (7,5-8 g/dl): le concentrazioni di ft4 e ft3 sono x2 quelle nel siero umano e vengono rilasciati dall'albumina. La concentrazione di ft4 e ft3 non è cambiata durante l'EVLP. La Steen ha alta fluorescenza per l'alta concentrazione delle molecole aromatiche (ormoni) mai descritto in precedenza. NADH e mtDNA nel perfused aumenta con danno ischemico e nel gruppo trattato con T3 Conclusione Il modello EVLP è già convalidato nella perfusione nel trapianto polmonare, ma è necessario approfondire l'effetto della Steen in termini di ormoni e analiti. L'effetto sull'IRI dell'EVLP sembra essere influenzato negativamente da un T3 troppo alto in Steen, cosa che descriviamo per la prima volta. L'ulteriore aggiunta di T3 provoca disfunzione mitocondriale e infiammazione.

Predictors Of Silent Myocardial Ischemia In Resistant Hypertensive Patients.

Hypertension is the most prevalent and significant modifiable risk factor for coronary heart disease. A portion of patients with uncontrolled hypertension are considered to have resistant hypertension (RHTN). Myocardial ischemia incidence increases along with blood pressure (BP) levels. However, the prevalence of myocardial ischemia in patients with RHTN, as well as the factors associated with it, is unknown. We enrolled 129 patients with true RHTN regularly followed in our specialty hypertension clinic and evaluated then by resting and dipyridamole pharmacological stress myocardial perfusion scintigraphy. Patients were then divided into 2 groups: those with (I-RHTN; n = 36) and those without (NI-RHTN; n = 93) myocardial ischemia. Echocardiography, 24-hour ambulatory BP monitoring (ABPM), and flow mediated dilation (FMD) were also evaluated. Thirty six (28%) patients had myocardial ischemia. There was no difference between groups regarding age, sex, biochemical parameters, office, and 24-hour ABPM levels. Patients in the I-RHTN group were more likely diabetic (31% vs. 11%; P < 0.05) and obese (75% vs. 40%; P < 0.001). Adjusting for age and body mass index, multiple logistic regression showed that diabetes (odds ratio (OR) = 6.5; 95% confidence interval (CI) = 1.06-40.14; P = 0.04), FMD (OR = 0.18; 95% CI = 0.07-0.41; P < 0.001), heart rate (OR = 1.23; 95% CI = 1.11-1.36; P < 0.001), left ventricular mass index (OR = 1.02; 95% CI = 1.01-1.04; P = 0.04), and microalbuminuria (OR = 1.02; 95% CI = 1.01-1.04; P = 0.002) were independent predictors of ischemia. In conclusion, there is a high prevalence of myocardial ischemia in patients with RHTN. Increased microalbuminuria, heart rate, endothelial dysfunction, and left ventricular mass can be useful to guide the investigation for myocardial ischemia in these high risk patients.

Brain SPECT imaging in Huntington's disease before and after therapy with olanzapine: case report

Olanzapine, an atypical antipsychotic drug, was administered to a patient with Huntington's disease (HD) with marked choreiform movements. Brain SPECT with 99mTc-HMPAO was performed before and after treatment. Brain SPECT imaging has been performed in patients with HD in order to determine the status of basal ganglia perfusion. The use of brain SPECT with 99mTc-HMPAO before and after treatment in patients with HD has not been yet reported. The marked hypoperfusion of the basal ganglia on brain SPECT performed before therapy with olanzapine improved significantly after treatment.

Efeitos da angiotensina-I e isquemia na recuperação funcional em corações isolados

FUNDAMENTO: A ressuscitação de parada cardíaca pode apresentar disfunção miocárdica determinada pelo tempo da isquemia, e a inibição da enzima conversora de angiotensina (ECA) pode reduzir a disfunção cardíaca durante a reperfusão. OBJETIVO: Investigar os efeitos da angiotensina-I e diferentes períodos de isquemia na recuperação funcional em corações de ratos isolados. MÉTODOS: Os corações isolados de ratos Wistar (n = 45; 250-300 g) foram submetidos a diferentes períodos de isquemia global (20, 25 ou 30 min) e reperfundidos (30 min) com o tampão Krebs-Henseleit, ou com a adição de 400 nmol/L de angiotensina-I, ou com 400 nmol/L de angiotensina-I + 100 µmol/L de captopril durante o período de reperfusão. RESULTADOS: A derivada positiva máxima de pressão (+dP/dt max) e o produto frequência-pressão foram reduzidos nos corações expostos à isquemia de 25 min (~ 73%) e à isquemia de 30 min (~ 80%) vs. isquemia de 20 min. A pressão diastólica final do ventrículo esquerdo (PDFVE) e a pressão de perfusão (PP) foram aumentadas nos corações expostos à isquemia de 25 min (5,5 e 1,08 vezes, respectivamente) e à isquemia de 30 min (6 e 1,10 vezes, respectivamente) vs. isquemia de 20 min. A angiotensina-I ocasionou uma diminuição no +dP/dt max e no produto frequência-pressão (~ 85-94%) em todos os períodos de isquemia e um aumento na PDFVE e na PP (6,9 e 1,25 vezes, respectivamente) apenas na isquemia de 20 min. O captopril foi capaz de reverter parcial ou completamente os efeitos da angiotensina-I na recuperação funcional nas isquemias de 20 e 25 min CONCLUSÃO: Os dados sugerem que a angiotensina-II participa direta ou indiretamente no dano pós-isquêmico e que a capacidade de um inibidor da ECA atenuar esse dano depende do tempo de isquemia.

Drag reduction by polyethylene glycol in the tail arterial bed of normotensive and hypertensive rats

This study was designed to evaluate the effect of drag reducer polymers (DRP) on arteries from normotensive (Wistar) and spontaneously hypertensive rats (SHR). Polyethylene glycol (PEG 4000 at 5000 ppm) was perfused in the tail arterial bed with (E+) and without endothelium (E-) from male, adult Wistar (N = 14) and SHR (N = 13) animals under basal conditions (constant flow at 2.5 mL/min). In these preparations, flow-pressure curves (1.5 to 10 mL/min) were constructed before and 1 h after PEG 4000 perfusion. Afterwards, the tail arterial bed was fixed and the internal diameters of the arteries were then measured by microscopy and drag reduction was assessed based on the values of wall shear stress (WSS) by computational simulation. In Wistar and SHR groups, perfusion of PEG 4000 significantly reduced pulsatile pressure (Wistar/E+: 17.5 ± 2.8; SHR/E+: 16.3 ± 2.7%), WSS (Wistar/E+: 36; SHR/E+: 40%) and the flow-pressure response. The E- reduced the effects of PEG 4000 on arteries from both groups, suggesting that endothelial damage decreased the effect of PEG 4000 as a DRP. Moreover, the effects of PEG 4000 were more pronounced in the tail arterial bed from SHR compared to Wistar rats. In conclusion, these data demonstrated for the first time that PEG 4000 was more effective in reducing the pressure-flow response as well as WSS in the tail arterial bed of hypertensive than of normotensive rats and these effects were amplified by, but not dependent on, endothelial integrity. Thus, these results show an additional mechanism of action of this polymer besides its mechanical effect through the release and/or bioavailability of endothelial factors.

Avaliação manométrica anal de crianças com encoprese

INTRODUÇÃO: A constipação crônica é doença comum na infância, ocorrendo em 5 a 10% dos pacientes pediátricos, considerada a segunda maior causa de procura nos consultórios de pediatria, sendo a encoprese decorrente de constipação grave associada à impactação fecal no reto. Dentre os exames diagnósticos, a manometria anal é utilizada para a avaliação de pacientes com distúrbios funcionais, como a constipação intestinal e a incontinência fecal, em alguns serviços para a avaliação de pacientes com encoprese, pois pode trazer informações sobre o mecanismo evacuatório e possíveis lesões esfincterianas anais. OBJETIVO: Verificar alterações manométricas em pacientes com encoprese. MÉTODOS: Foi realizado estudo de 40 manometrias anais de crianças constipadas com encoprese (G1) e 12 crianças constipados sem encoprese (G2). Foram obtidos os seguintes dados: pressões de repouso, contração e evacuação do canal anal e ampola retal, ponto de maior pressão, reflexo inibitório anal e sensibilidade retal. As manometrias foram realizadas com o aparelho Alacer de perfusão com 8 canais. RESULTADOS: Não foram encontradas diferenças nas pressões de repouso, contração e evacuação do canal anal entre os grupos. Chamou-nos a atenção a ausência de necessidade de maior volume retal para desencadear o reflexo inibitório anal. Não houve diferença da incidência de anismus entre os dois grupos, demonstrando que não se trata de fator importante na manutenção da encoprese, mas sim da constipação. CONCLUSÃO: Não houve necessidade de maior volume para desencadear o reflexo inibitório anal. O anismus não foi diferente entre os dois grupos, não sendo importante na manutenção da encoprese.

Avaliação cintilográfica de diferentes dosagens de Tecnécio-99m na padronização da perfusão pulmonar em cães da raça Rottweiller

A avaliação da função pulmonar em cães pode ser obtida mediante exames cintilográficos, os quais incluem a injeção de radiofármacos, seguida de radiografias. Neste estudo, foram utilizados 10 cães machos hígidos da raça Rottweiler e radiograficamente normais e soronegativos para dirofilariose, com administração de doses variadas de macroagregado de albumina sérica humana marcados com tecnécio-99m ([99mTc](MAA)). Os resultados foram avaliados qualitativa e quantitativamente, considerando o índice de perfusão pulmonar e sua homogeneidade, sendo dessa maneira visualizado um aumento na homogeneidade da imagem diretamente relacionado ao número de partículas de MAA injetado. Este estudo define os critérios de normalidade e de dosagem na perfusão pulmonar em cães hígidos da raça Rottweiller estabelecidos com a técnica de cintilografia.

Renal hypothermia: Experience in pigs and clinical trial

Purpose: This study was designed to compare the effectiveness of two methods of inducing renal hypothermia through laparoscopy in pigs and humans. Materials and Methods: Twelve pigs were divided into four groups of three animals each. Both kidneys of the animals in Groups A, B, and C were submitted to pelvic irrigation with cold saline (4 degrees C) for 20 minutes, with flow rates of 5 mL/min, 10 mL/min, and 15 mL/min, respectively. In Group D renal hypothermia was induced by intracorporeal ice slush applied to the surface for 20 minutes. All maneuvers were performed laparoscopically and renal cortex temperature was measured by a thermocouple needle. Five human patients also underwent laparoscopic partial nephrectomy due to renal cell carcinoma. In one case renoprotection was induced by retrograde endoscopic cold saline perfusion at a flow rate of 10 mL/min. In the remaining four patients we induced renal hypothermia via laparoscopic application of ice slush. The renal temperature of the human patients was also monitored using a thermocouple needle. Results: In the pigs, at 20 minutes of renal pelvis perfusion the mean renal temperature, the temperature drop, and saline flow per gram of kidney were: Group A, -29.5 degrees C +/- 1.1 (-6.3 degrees C; 0.10 mL); Group B, -22.8 degrees C +/- 1.1 (-13.1 degrees C; 0.22 mL); and Group C, -21.1 degrees C +/- 0.9 (-14.9 degrees C; 0.31 mL). In Group D the mean renal cortex temperature at 20 minutes was 13.6 degrees C +/- 1.2, a drop of -22.5 degrees C. There were striking differences among the groups (P < 0.0001). The laparoscopic partial nephrectomy was uneventful in all five human patients. The lowest renal cortex temperature was 32.5 degrees C, seen in the patient who submitted to pelvic irrigation with cold saline, and the mean temperature drop was 19.1 degrees C +/- 2.5 degrees C in the patients who submitted to ice slush-induced renal hypothermia. Conclusions: Induction of renal hypothermia using intracorporeal ice slush confers lower kidney temperatures than endoscopically-induced cold saline perfusion.