Regensburg, Univ., Diss., 2009.

A esquizofrenia continua sendo um dos transtornos mais desafiadores para a clínica psiquiátrica, apesar dos avanços dos estudos que tentam elucidar sua fisiopatologia e buscam novas opções de tratamento, isto impulsionado pela eficácia limitada dos atuais antipsicóticos utilizados no tratamento de tal transtorno. A pregabalina é uma nova droga antiepiléptica, também usada para controle de dores neuropáticas pós-herpéticas, dores neuropáticas diabéticas, fibromialgia, e recentemente aprovada para o tratamento de transtornos ansiosos. Tem como provável mecanismo de ação um incremento na função gabaérgica, apesar de não interagir com receptores gabaérgicos, pois atua através de sua ligação com a subunidade 2 dos canais de cálcio neuronais, diminuindo assim a liberação de neurotransmissores. Frente às evidências da existência de uma eficácia provável da pregabalina em sintomas psicóticos, ao menos como adjuvante, e do crescente interesse terapêutico no uso da mesma em diferentes transtornos, justifica-se um estudo que envolva pacientes esquizofrênicos utilizando tal medicação. Nas duas últimas décadas, o estudo dos mecanismos neurobiológicos subjacentes aos transtornos psiquiátricos, bem como a investigação dos possíveis mecanismos e regiões cerebrais influenciadas por substâncias psicofarmacológicas, recebeu importante contribuição das técnicas de neuroimagem funcional. Apesar disto, até o momento não existe nenhum estudo que procurou avaliar os mecanismos centrais relacionados às propriedades ansiogênicas e/ou ansiolíticas, bem como anticonvulsivantes e analgésicas da pregabalina em humanos. Assim, o presente estudo tem como objetivo investigar os efeitos da pregabalina no fluxo sangüíneo cerebral em 20 portadores de esquizofrenia, utilizando tomografia por emissão de fóton único - SPECT, em um estudo cruzado, duplo-cego, controlado por placebo. A avaliação de alterações psicopatológicas dos voluntários durante a ação da pregabalina foi feita com a Escala Breve de Avaliação Psiquiátrica- Brief Psychiatric Rating Scale-BPRS, os estados subjetivos secundários à ação da pregabalina foram avaliados com a Visual Analogic Mood Scale VAMS. O resultado das imagens mostra alterações significativas de perfusão em estruturas que compõem via glutamatérgica (pré-frontal-temporal-tálamo) com principal diminuição de ativação no córtex frontal superior. Houve aumento de ativação em estruturas relacionadas à motricidade (giro pré-central e áreas do cerebelo tuber, uncus, culmen). Os dados apóiam a hipótese de que a pregabalina age modulando neurotransmissores nestas regiões e sistemas. A pregabalina apresenta potencial no tratamento de sintomas ansiosos de pacientes psicóticos. / Schizophrenia remains as one of the most challenging disorders to psychiatry in spite of advances achieved by studies attempting to elucidate its physiopathology and find for new options of treatment, considering the limited efficacy of current antipsychotic medication used in the treatment of this disorder. Pregabalin is a novel antiepileptic drug which is also used in the treatment and control of post-herpetic neuropathic pain, diabetic neuropathic pain and fibromyalgia, and it has recently been approved for the treatment of anxiety disorders. Its possibly acts through the increase in the gabaergic function, although it doesn\'t interact directly with gabaergic receptors, it acts on 2 subunits of neuronal calcium channel, thus decreasing the release of neurotransmitters. The present study was considered relevant due to the evidence of a possible efficacy of pregabalin on psychotic symptoms, at least as add-on treatment, and the increased therapeutic interest concerning the use of the drug in different disorders. In the past two decades the neurobiological mechanisms related to psychiatric disorders as well as the investigation of possible mechanisms and brain regions influenced by pharmacological substances received important technical contributions from functional neuroimage techniques. However, currently, there are no studies evaluating the mechanisms related to the anxiogenic and/or anxiolytic, and anticonvulsant and analgesic properties of pregabalin in humans. Therefore, the present study aimed to investigate the effects of pregabalin in the cerebral brain flow of 20 patients with schizophrenia, using single photon emission tomography SPECT, in a crossed double-blind placebo controlled study. Psychopathological alterations during the use of pregabalin was performed with the Brief Psychiatric Rating Scale-BPRS, subjective state was evaluated with Visual Analogic Mood Scale VAMS. Image analysis shows significant hipoperfusion in structures of the glutamatergic pathway (pré-frontal-temporal-thalamus), with main hipoactivation in the superior frontal cortex. There has been an increase of activation in motor areas (the precentral gyrus and cerebellar structures tuber, uncus, culmen). Data analysis supports the hypothesis that pregabalin acts by modulating neurotransmitters in these areas. Pregabalin shows potential for the treatment of anxiety in psychotic patients.

A esquizofrenia continua sendo um dos transtornos mais desafiadores para a clínica psiquiátrica, apesar dos avanços dos estudos que tentam elucidar sua fisiopatologia e buscam novas opções de tratamento, isto impulsionado pela eficácia limitada dos atuais antipsicóticos utilizados no tratamento de tal transtorno. A pregabalina é uma nova droga antiepiléptica, também usada para controle de dores neuropáticas pós-herpéticas, dores neuropáticas diabéticas, fibromialgia, e recentemente aprovada para o tratamento de transtornos ansiosos. Tem como provável mecanismo de ação um incremento na função gabaérgica, apesar de não interagir com receptores gabaérgicos, pois atua através de sua ligação com a subunidade 2 dos canais de cálcio neuronais, diminuindo assim a liberação de neurotransmissores. Frente às evidências da existência de uma eficácia provável da pregabalina em sintomas psicóticos, ao menos como adjuvante, e do crescente interesse terapêutico no uso da mesma em diferentes transtornos, justifica-se um estudo que envolva pacientes esquizofrênicos utilizando tal medicação. Nas duas últimas décadas, o estudo dos mecanismos neurobiológicos subjacentes aos transtornos psiquiátricos, bem como a investigação dos possíveis mecanismos e regiões cerebrais influenciadas por substâncias psicofarmacológicas, recebeu importante contribuição das técnicas de neuroimagem funcional. Apesar disto, até o momento não existe nenhum estudo que procurou avaliar os mecanismos centrais relacionados às propriedades ansiogênicas e/ou ansiolíticas, bem como anticonvulsivantes e analgésicas da pregabalina em humanos. Assim, o presente estudo tem como objetivo investigar os efeitos da pregabalina no fluxo sangüíneo cerebral em 20 portadores de esquizofrenia, utilizando tomografia por emissão de fóton único - SPECT, em um estudo cruzado, duplo-cego, controlado por placebo. A avaliação de alterações psicopatológicas dos voluntários durante a ação da pregabalina foi feita com a Escala Breve de Avaliação Psiquiátrica- Brief Psychiatric Rating Scale-BPRS, os estados subjetivos secundários à ação da pregabalina foram avaliados com a Visual Analogic Mood Scale VAMS. O resultado das imagens mostra alterações significativas de perfusão em estruturas que compõem via glutamatérgica (pré-frontal-temporal-tálamo) com principal diminuição de ativação no córtex frontal superior. Houve aumento de ativação em estruturas relacionadas à motricidade (giro pré-central e áreas do cerebelo tuber, uncus, culmen). Os dados apóiam a hipótese de que a pregabalina age modulando neurotransmissores nestas regiões e sistemas. A pregabalina apresenta potencial no tratamento de sintomas ansiosos de pacientes psicóticos. / Schizophrenia remains as one of the most challenging disorders to psychiatry in spite of advances achieved by studies attempting to elucidate its physiopathology and find for new options of treatment, considering the limited efficacy of current antipsychotic medication used in the treatment of this disorder. Pregabalin is a novel antiepileptic drug which is also used in the treatment and control of post-herpetic neuropathic pain, diabetic neuropathic pain and fibromyalgia, and it has recently been approved for the treatment of anxiety disorders. Its possibly acts through the increase in the gabaergic function, although it doesn\'t interact directly with gabaergic receptors, it acts on 2 subunits of neuronal calcium channel, thus decreasing the release of neurotransmitters. The present study was considered relevant due to the evidence of a possible efficacy of pregabalin on psychotic symptoms, at least as add-on treatment, and the increased therapeutic interest concerning the use of the drug in different disorders. In the past two decades the neurobiological mechanisms related to psychiatric disorders as well as the investigation of possible mechanisms and brain regions influenced by pharmacological substances received important technical contributions from functional neuroimage techniques. However, currently, there are no studies evaluating the mechanisms related to the anxiogenic and/or anxiolytic, and anticonvulsant and analgesic properties of pregabalin in humans. Therefore, the present study aimed to investigate the effects of pregabalin in the cerebral brain flow of 20 patients with schizophrenia, using single photon emission tomography SPECT, in a crossed double-blind placebo controlled study. Psychopathological alterations during the use of pregabalin was performed with the Brief Psychiatric Rating Scale-BPRS, subjective state was evaluated with Visual Analogic Mood Scale VAMS. Image analysis shows significant hipoperfusion in structures of the glutamatergic pathway (pré-frontal-temporal-thalamus), with main hipoactivation in the superior frontal cortex. There has been an increase of activation in motor areas (the precentral gyrus and cerebellar structures tuber, uncus, culmen). Data analysis supports the hypothesis that pregabalin acts by modulating neurotransmitters in these areas. Pregabalin shows potential for the treatment of anxiety in psychotic patients.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Programa de Formación de Especialista en Medicina Nuclear / El SPECT gatillado de perfusión miocárdica es una técnica ampliamente usada para la detección de isquemia, valorar la respuesta al tratamiento, estratificar el riesgo, establecer un pronóstico, evaluar el tamaño de un infarto e investigar la viabilidad. Adicionalmente, aporta información útil sobre la función ventricular mediante el cálculo de la fracción de eyección del ventrículo izquierdo (FEVI) así como la estimación de su volumen y motilidad gracias a los diferentes softwares desarrollados con este fin. El año 2005 se introdujo el análisis de fase de los estudios SPECT de perfusión miocárdica gatillado con onda R de señal electrocardiográfica para la investigación de la disfunción mecánica del ventrículo izquierdo (VI), permitiendo así el estudio simultáneo de perfusión, función y sincronía de la contracción miocárdica. Debido al gran desarrollo de modalidades de diagnóstico y tratamiento de la enfermedad coronaria (EC) durante las últimas décadas, cada vez más pacientes logran sortear los episodios agudos y llegar a etapas más evolucionadas de su patología, donde muchos fallecen por insuficiencia cardíaca. Últimamente algunos trabajos han planteado que la isquemia miocárdica puede alterar la sincronía intraventricular izquierda, pudiendo corresponder a un parámetro adicional y precoz, lo cual es una alternativa muy interesante y de bajo costo, que incluso pudiera ser independiente de la presencia de las alteraciones de perfusión. Hipótesis: Con la técnica SPECT y adquisición gatillada tardía con Dipiridamol el análisis de fase de contracción del VI encuentra parámetros de sincronía similares en reposo y post estrés tanto en casos con perfusión normal o anormal independiente del grado de isquemia. Objetivo principal: Conocer si los pacientes con isquemia miocárdica en SPECT de perfusión cardíaca con Tc99m-Sestamibi posterior a estrés farmacológico con Dipiridamol con adquisición tardía, presentan alteraciones significativas en el histograma de fase de contracción del VI. Objetivo Secundario: Evaluar análisis de disincronía por género, edad y función del VI medida con parámetros del gatillado en software comercial en todos los casos de estrés realizado con vasodilatador. Materiales y métodos: Estudio retrospectivo de pacientes derivados para estudio de SPECT gatillado de perfusión miocárdica en un Hospital Universitario. Se obtuvo aprobación del comité ético científico de la institución. Se evaluó la perfusión miocárdica, cuantificación mediante software QPS® y análisis de función gatillada con sofware QGS®. Además se realizó análisis de fase utilizando para ello la herramienta Synctool® del software Emory Cardiac Toolbox®. Los pacientes fueron clasificados según los resultados de la perfusión del SPECT miocárdico en normal, presencia de defecto transitorio, defecto fijo y aquellos portadores de defectos de perfusión de tipo mixto (isquemia e infarto). De los estudios evaluados, se eligieron sólo aquellos en que la prueba de estrés fue efectuada con dipiridamol; de éstos se separaron los pacientes que no presentaron defectos de perfusión y aquellos que mostraron hallazgos reversibles compatibles con isquemia. Mediante método semiautomático se evaluaron parámetros cuantitativos del análisis de fase de la contracción del VI [peak, ancho de banda (BW), desviación estándar (SD), skewness, kurtosis del histograma de contracción del VI]. Se compararon estos resultados entre estrés y reposo para los pacientes con isquemia pura en el SPECT miocárdico y también en ambas fases entre pacientes con perfusión normal e isquémicos. Se consideró significativo un valor p <0,05 Resultados: De 208 estudios SPECT de perfusión miocárdica en fases de estrés y reposo, 171 fueron realizados con dipiridamol, 56.7% hombres y 43.3% mujeres; en el grupo completo 56.1% tenían perfusión normal, 19.9% defecto de perfusión transitorio, 19.3% defecto fijo y 4.7% defecto mixto. De los 34 casos con defectos transitorios (isquemia pura) no hubo diferencias significativas de los parámetros de sincronía evaluados entre estrés farmacológico y reposo, siendo además comparables con los resultados obtenidos en los pacientes sin defectos de perfusión. Se encontró buena correlación entre SD y BW con parámetros funcionales (FEVI y EDV) en el grupo completo y no hubo diferencias significativas entre los promedios por género ni tampoco en los mayores y menores de 65 años del grupo total de exámenes realizados con dipiridamol. Conclusión: El protocolo de adquisición con estrés farmacológico no inmediato postestrés, no altera los índices de disincronía mecánica en el análisis de fase intraventricular izquierdo, y no permite pesquisar isquemia en forma precoz. Esto puede explicarse porque las imágenes son adquiridas al menos 45 minutos después de la inyección del trazador durante la prueba de esfuerzo en que el atontamiento isquémico se ha reducido considerablemente.

SPECT as a representative of molecular imaging allows visualization of metabolic processes in vivo. In clinical practice, single photon emission imaging is an established modality for myocardial perfusion imaging or the diagnosis of adrenal or neuroendocrine tumors, to name a few. With technical advances in scanner design and data processing leading to improved spatial resolution and image quality, SPECT has become a serious contender in small animal preclinical imaging. With multi-pinhole collimation, submillimeter spatial resolutions are achieved without limiting sensitivity, which has led to a significant increase of interest in SPECT for preclinical research in recent years. In this dissertation, the potential of a two-detector system through an analysis of three dedicated mouse collimators with multi-pinhole configurations was demonstrated. For this, sensitivity, spatial resolution, and uniformity as key parameters were determined. In the second part of the present work, an evaluation of the image quality at different activity concentrations to allow prediction of the system performance related to in vivo studies was performed. Therefore, a visual evaluation, as well as a calculation of the contrastto-noise ratio, was performed using mini Derenzo phantoms for the respective three mouse collimators. To better classify the results, the study was extended by a comparison with the predecessor system. Due to the absence of the third bottom detector, sensitivity and uniformity are slightly compromised. All three collimators were able to achieve a spatial resolution in the submillimeter range, XUHR-M offers a peak resolution of up to 0.35 mm. In terms of resolution, both evaluated systems performed on an equal level. Visual assessment of image quality indicates a slight advantage of the new two-detector system, and the contrast-to-noise ratio seems to benefit from the improved SROSEM algorithm. However, the differences between the two systems are marginal. The U-SPECT5/CT E-Class is proven to be state-of-the-art for small animal imaging and is a powerful instrument for preclinical molecular imaging research. Improvements in system design compensate well for the reduction in the detection area, allowing excellent imaging even with low activity concentrations. / SPECT als Vertreter der molekularen Bildgebung ermöglicht die Visualisierung von Stoffwechselprozessen in vivo. In der klinischen Praxis ist die Einzelphotonen-Emissions-Bildgebung eine etablierte Modalität für die Myokard-Perfusions-Bildgebung oder die Diagnose von Nebennieren- oder neuroendokrinen Tumoren, um nur einige Beispiele zu nennen. Mit den technischen Fortschritten bei der Konstruktion von Scannern und der Datenverarbeitung, die zu einer verbesserten räumlichen Auflösung und Bildqualität führen, ist SPECT zu einem ernstzunehmenden Mitbewerber in der präklinischen Bildgebung von Kleintieren geworden. Unter der Verwendung von Multipinhole-Kollimatoren lassen sich Ortsauflösungen von unter einem Millimeter erzielen, ohne die Sensitivität deutlich einzuschränken. Dies trug dazu bei, dass das Interesse an SPECT in der präklinischen Forschung in den letzten Jahren zugenommen hat. In dieser Dissertation wurde das Potenzial eines Zweidetektorsystems unter Verwendung von drei Multipinhole-Mauskollimatoren evaluiert. Zur Leistungsbewertung wurde Sensitivität, Ortsauflösung und Homogenität bestimmt. Im zweiten Teil dieser Arbeit wurde eine Analyse der Bildqualität mit verschiedenen Aktivitätskonzentrationen durchgeführt, um eine Vorhersage der Leistung des Systems in In-vivo-Studien zu ermöglichen. Dazu wurde eine visuelle Bewertung sowie eine Berechnung des Kontrast-zu-Rausch-Verhältnisses mit Mini-Derenzo-Phantomen für die entsprechenden drei Mauskollimatoren durchgeführt. Um die Ergebnisse besser einordnen zu können, wurde die Studie um einen Vergleich mit dem Vorgängersystem erweitert. Durch das Fehlen des dritten unteren Detektors sind Sensitivität und Homogenität leicht beeinträchtigt. Alle drei Kollimatoren konnten eine Ortsauflösung unter einem Millimeter erreichen, wobei XUHR-M die höchste Auflösung von bis zu 0.35 mm erreicht. Die beiden untersuchten Systeme sind hinsichtlich der Ortsauflösung gleichwertig. Die visuelle Bewertung der Bildqualität deutet auf einen leichten, jedoch nur marginalen Vorteil des neuen Zweidetektorsystems hin, und das Kontrast-zu-Rausch-Verhältnis scheint von dem verbesserten SROSEM-Algorithmus zu profitieren. Das U-SPECT5/CT E-Class ist nachweislich auf dem neuesten Stand der Technik für die Bildgebung bei Kleintieren und ein leistungsfähiges Instrument für die präklinische Forschung. Das System kompensiert die Reduktion der Detektionsfläche und ermöglicht eine hervorragende Bildgebung auch bei geringen Aktivitätskonzentrationen.

A new class of scintillation detector has emerged that combines columnar scintillators and CCD/CMOS sensors for high-resolution imaging. Originally developed for single-photon gamma-ray imaging, these detectors provide better than an order-of-magnitude improvement in spatial resolution compared to conventional photomultiplier tube (PMT)-based gamma cameras; sub-100 micron detector resolutions have been achieved. This work reviews the several detector configurations developed in recent years, with a specific emphasis on a type of CCD/CMOS detector developed at the Center for Gamma-Ray Imaging, which we call BazookaSPECT, that amplifies scintillation light using an image intensifier to achieve both high spatial resolution and high event-rate capability.Ongoing research into scintillator deposition techniques has led to a new form of scintillation material where crystallites are organized into columns. Similar to optical fibers, this columnar structure helps to channels scintillation light towards an exit face while restricting lateral light spread. However, because they are not perfect optical fibers, light spreads laterally and is absorbed by an amount relating to the interaction depth. Taking advantage of this phenomenon, we discuss the use of maximum-likelihood methods to estimate the 3D position and energy of gamma-ray interactions in columnar CsI(Tl)/EMCCD-based detectors.Finally, we present new imaging applications that have arisen from BazookaSPECT. These include the the development of a gamma-ray microscope using micro-coded apertures, feasibility studies for photon-counting digital mammography and eventually X-ray CT, and FastSPECT III -- a third generation small animal stationary SPECT imager. FastSPECT III system design, fabrication methods, data acquisition system, system calibration procedure, and initial tomographic reconstructions are presented.

<p>The overall goal of this dissertation is to optimize and evaluate the performance of the single photon emission computed tomography (SPECT) subsystem of a dedicated three-dimensional (3D) dual-modality breast imaging system for enhanced semi-automated, quantitative clinical imaging. This novel hybrid imaging system combines functional or molecular information obtained with a SPECT subsystem with high-resolution anatomical imaging obtained with a low dose x-ray Computed Tomography (CT) subsystem. In this new breast imaging paradigm, coined "mammotomography," the subject is imaged lying prone while the individual subsystems sweep 3-dimensionally about her uncompressed, pendant breast, providing patient comfort compared to traditional compression-based imaging modalities along with high fidelity and information rich images for the clinician. </p><p> System evaluation includes a direct comparison between dedicated 3D SPECT and dedicated 2D scintimammography imaging using the same high performance, semi-conductor gamma camera. Due to the greater positioning flexibility of the SPECT system gantry, under a wide range of measurement conditions, statistically significantly (p<0.05) more lesions and smaller lesion sizes were detected with dedicated breast SPECT than with compressed breast scintimammography. The importance of good energy resolution for uncompressed SPECT breast imaging was also investigated. Results clearly illustrate both visual and quantitative differences between the various energy windows, with energy windows slightly wider than the system resolution having the best image contrast and quality.</p><p> An observer-based contrast-detail study was performed in an effort to evaluate the limits of object detectability under various imaging conditions. The smallest object detail was observed using a 45-degree tilted trajectory acquisition. The complex 3D projected sine wave acquisition, however, had the most consistent combined intra and inter-observer results, making it potentially the best imaging approach for consistent clinical imaging.</p><p> Automatic ROR contouring is implemented using a dual-layer light curtain design, ensuring that an arbitrarily shaped breast is within ~1 cm of the camera face, but no closer than 0.5 cm at every projection angle of a scan. Autocontouring enables simplified routine scanning using complex 3D trajectories, and yields improved image quality. Absolute quantification capabilities are also integrated into the SPECT system, allowing the calculation of in vivo total lesion activity. Initial feasibility studies in controlled low noise experiments show promising results with total activity agreement within 10% of the dose calibrator values.</p><p> The SPECT system is integrated with a CT scanner for added diagnostic power. Initial human subject studies demonstrate the clinical potential of the hybrid SPECT-CT breast imaging system. The reconstructed SPECT-CT images illustrate the power of fusing functional SPECT information to localize lesions not easily seen in the anatomical CT images. Enhanced quantitative 3D SPECT-CT breast imaging, now with the ability to dynamically contour any sized breast, has high potential to improve detection, diagnosis, and characterization of breast cancer in upcoming larger-scale clinical testing.</p> / Dissertation

The aim of this work is the assessment of the diagnostic accuracy in parathyroid glands (PG) detection by various scintigraphic methods and to propose the optimal examination procedure for successful localization of hyperfunctional PG. The patients were divided into 3 groups with individual types of hyperparathyroidism (HPT): group I. primary PHPT (253 patients), group II. normocalcemic NPHPT (75 patients) and group III. secondary SHPT (61 patients). For all the patients protocol A was performed: one day a two-phase SPECT/CT scan using 99mTc-MIBI (technetium 2-methoxyisobutylisonitrile) depicted simultaneously thyroid gland and PG, and another day thyroid SPECT using 99mTc-NaTcO4 (pertechnetate) for 3D subtraction analysis. In case of 44 patients from group I with negative or unclear results of the protocol A also protocol B was performed: PET/CT using 18F-FCH (fluorocholine). The results of surgery and histology served as a "gold standard" for the assessment of the accuracy of scintigraphic findings. In group I. 209/253 patients had a positive finding on scintigraphy using protocol A and 44 patients with an unclear or negative finding of protocol A underwent protocol B examination. In total, 253 patients were operated. The results of the diagnostic accuracy: sensitivity, specificity, positive...

ABSTRACT Trichotillomania was first defined over a hundred years ago as a self inflicted alopecia resulting from avulsion of hair. Previous Positron Emission Tomography (PET) studies have shown increased count density in the right superior parietal region of patients suffering from trichotillomania. It is unclear if this increase in count density might be a state or trait related marker of the disease. Research has indicated that Cognitive Behaviour Therapy can systematically modify cerebral metabolic activity which is significantly related to clinical outcome. In the case of Obsessive Compulsive Disorder (OCD), a decrease of metabolic activity has been demonstrated using Pet. The present study was undertaken to investigate whether similar metabolic changes as indicated by Single Beam Positron Emission Computerised Tomography. (SPECT), will be found in trichotillomania after Cognitive Behaviour Therapy. Twelve patients diagnosed as suffering from trichotillomania, using DSM-IV criteria, underwent brain SPECT scanning using 99mTc-HMPAO. Scanning was performed before and after Cognitive Behaviour Therapy intervention. The psychotherapy was conducted in 12-16 sessions. The response to Cognitive Behaviour Therapy was assessed using the Psychiatric Institute Trichotillomania Scale and the Hamilton Anxiety Rating Scale. Ratings were completed at the beginning and end of the trial. The analysis of the scan data was done by comparing the left to the right superior parietal region. For each patient the region of interest was applied on the superior transaxial brain slices where the cingulate gyrus fully appeared. Each region of interest had the average number of counts normalised to the maximal cerebellar uptake. Baseline studies showed a significant increased count of 99mTc-HMPAO in the right superior parietal areas compared to the same areas on the left (p<0.0003). This pattern normalised after Cognitive Behaviour Therapy, such that there was no significant difference between the right and left superior parietal areas in those patients who responded (n=9) to therapy. In the non-responder group (n=3), the pattern remained unchanged. Using SPECT this study confirms previous reports of increased density in the right superior parietal lobe. In addition, it suggests that the increased count of 99mTc-HMPAO in the right parietal area is a state related disturbance in neurophysiology in this disorder, as it resolves with successful treatment. Of substantial importance is the fact that this study demonstrates a neurophysiological substrate and impact of psychotherapy. In conclusion this data suggests that the increased count density in the right superior parietal area is a state related marker of trichotillomania. 99mTc-HMPAO brain SPECT can therefore be used to monitor therapy of patients suffering from this disease.