Neuroimaging of Dopamine Transporter Density in the Striatum of Disordered Gamblers.

The aim of the present research was to add to the growing literature on dopamine and gambling disorder (GD) by assessing whether GD is associated with dopamine transporter (DAT) density in the ventral striatum compared to healthy controls and whether DAT density was associated with key characteristics of GD (e.g., abstinence, craving). In a cross-sectional investigation using single-photon emission computed tomography with a technetium-99m-labeled tropane derivative as a radiotracer with SPECT imaging, fifteen participants with GD and 15 controls (non-gambling individuals, matched for age, gender, handedness, and smoking status) were measured. The GD group completed self-reported questionnaires regarding gambling. Striatal DAT density did not differ between the two groups. Conversely, striatal DAT density correlated significantly with various measures of recent gambling, but not with measures of chronic gambling. Multivariate analysis, adjusted for age and smoking status, showed that DAT density in the left striatum correlated positively with time spent gambling and gambling craving in the last month, whereas DAT density in the right striatum correlated negatively with abstinence self-efficacy. The results suggests that DAT density in the striatum is associated with recent gambling activity and gambling expectation.

Case 241: Hemiparkinsonism- Hemiatrophy-SPECT with 99mTc TRODAT-1 and Muscle MR Imaging Abnormalities.

History A 43-year-old right-handed man presented with a history of progressive mild left-sided weakness and slowness of movements. Symptoms began 4 years earlier, and the patient noticed a progressive decline in his daily routine due to gait difficulties in the past year. There was no history of head trauma, surgery, drug therapy, smoking, or alcohol abuse, nor was there any relevant family history. Examination revealed normal cognition (29 of 30 points on the Mini-Mental State Examination and 27 of 30 points on the Montreal Cognitive Assessment) and normal cerebellar, sensory, cranial nerve, and autonomic function. There was mild left-sided weakness involving the upper and lower limbs (medical research council graded muscle strength as 4+ out of 5) that was associated with facial hypomimia and a rigid akinetic syndrome only in the patient's left hemibody (Unified Parkinson's Disease Rating Scale [UPDRS] part III [motor examination], 23 out of 52 points). Mild atrophy in the left upper and lower limbs without pain, swelling, or skin lesions was noted at physical examination. Routine blood chemistry was normal, as were serum creatine kinase and aldolase levels and thyroid, hepatic, and renal function. T1- and T2-weighted, fluid-attenuated inversion recovery, diffusion- and perfusion-weighted, and contrast material-enhanced brain magnetic resonance (MR) imaging results were normal, without basal ganglia hyperintensity, lacunae, calcification, or heavy metal deposits. Muscle MR imaging and single photon emission computed tomography (SPECT) with technetium 99m (99mTc) tropane dopamine transporter (TRODAT)-1 were performed for further evaluation. This patient received levodopa and benserazide (200 and 50 mg, respectively) four times a day and amantadine (100 mg) three times a day without adequate improvement (UPDRS score decreased from 23 to 20 points).

The effectiveness of acupuncture as a treatment for tinnitus: a randomized controlled trial using (99m)Tc-ECD SPECT.

OBJECTIVE: Investigate the effect of acupuncture on brain perfusion using ethyl cysteinate dimer single-photon emission computed tomography ((99m)Tc-ECD SPECT) in patients with tinnitus. METHODS: This randomized, single-blind, sham-control study examined patients (18-60 years old) with normal hearing and chronic, idiopathic, continuous tinnitus. Fifty-seven subjects were randomly assigned to true (n = 30) or sham (n = 27) acupuncture (ACP); (99m)Tc-ECD SPECT examinations were performed before and after 12 twice-weekly ACP sessions. Secondary outcomes included changes in the Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), Hamilton Anxiety Scale (HAS) and Beck Depression Inventory (BDI). Imaging data were analysed using Statistical Parametric Mapping (SPM8) software. Regression models were used to examine secondary outcomes via two paradigms: intention-to-treat (ITT; where multiple imputations were conducted because of study attrition) and complete cases. RESULTS: No between-group brain perfusion differences were observed. However, a significant improvement in THI scores was observed at the end of true ACP treatment for all domains (all p values < 0.01) except the catastrophic scale. CONCLUSIONS: ACP might reduce the effects of tinnitus on daily life; however, additional studies should be conducted to verify the effects of ACP on the neural architecture and brain function of tinnitus patients. KEY POINTS: • Efficacy of acupuncture on brain perfusion and symptoms of tinnitus patients. • Acupuncture improved the Tinnitus Handicap Inventory scores in tinnitus patients. • No significant changes in brain perfusion were observed after 12 twice-weekly sessions. • Perfusion changes would reflect changes in neuronal function.

Neurophysiological studies and non-motor symptoms prior to ataxia in a patient with machado-joseph disease: trying to understand the natural history of brain degeneration.

Spinocerebellar ataxia type 3 or Machado-Joseph disease is the most common spinocerebellar ataxia. In this neurological disease, anatomical, physiological, clinical, and functional neuroimaging demonstrate a degenerative process besides the cerebellum. We performed neurophysiological and neuroimaging studies-polysomnography, transcranial sonography, vestibular-evoked myogenic potential, single-photon emission computed tomography (SPECT) with (99m)Tc-TRODAT-1, and a formal neuropsychological evaluation in a patient with sleep complaints and positive testing for Machado-Joseph disease, without cerebellar atrophy, ataxia, or cognitive complaints. Polysomnography disclosed paradoxical high amplitude of submental muscle, characterizing REM sleep without atonia phenomenon. Transcranial sonography showed hyperechogenicity of the substantia nigra. There was an absence of vestibular-evoked myogenic potentials on both sides in the patient under study, in opposite to 20 healthy subjects. Brain imaging SPECT with (99m)Tc-TRODAT-1 demonstrated a significant lower DAT density than the average observed in six healthy controls. Electroneuromyography was normal. Neuropsychological evaluation demonstrated visuospatial and memory deficits. Impairment of midbrain cholinergic and pontine noradrenergic systems, dysfunction of the pre-synaptic nigrostriatal system, changes in echogenicity of the substantia nigra, and damage to vestibulo-cervical pathways are supposed to occur previous to cerebellar involvement in Machado-Joseph disease.

Dopamine transporter imaging using 99mTc-TRODAT-1 SPECT in Parkinson's disease.

BACKGROUND: Although the decrease in striatal dopamine transporter (DAT) density has been described in North American, European, and Asian Parkinson's disease (PD) patients, studies on this issue are required in the rest of the world. This study examined the diagnostic utility of DAT imaging in Brazilian PD patients. MATERIAL/METHODS: Twenty PD patients (13 males, 7 females, median age: 62 years, median age at disease onset: 56 years, median disease duration: 5 years, and median UPDRS-III score: 29) and 9 age- and sex-matched healthy subjects underwent single-photon emission computerized tomography (SPECT) using 99mTc-TRODAT-1. RESULTS: PD patients showed a significant decrease in the striatum, caudate nucleus, and putamen DAT densities compared with data from healthy subjects. Striatal 99mTc-TRODAT-1 bindings had the highest diagnostic accuracy compared to those estimates from caudate nucleus and putamen. For the diagnosis of PD, a striatal 99mTc-TRODAT-1 binding cut-off value of 0.90 was associated with a sensitivity of 100% and a specificity of 89%. There was no significant difference between striatal 99mTc-TRODAT-1 binding values provided by different readers, contrary to 99mTc-TRODAT-1 binding estimates in the caudate nucleus. CONCLUSIONS: Striatal DAT imaging using 99mTc-TRODAT-1 can be considered a marker for differentiating PD patients from healthy individuals, with a good interobserver reproducibility.

Combined assessment by transcranial sonography and Sniffin' Sticks test has a similar diagnostic accuracy compared to brain SPECT for Parkinson's disease diagnosis.

OBJECTIVES: This study aimed to investigate the accuracy of TCS combined with the Sniffin' sticks olfactory test (SST-16) for differentiation between idiopathic PD patients and healthy controls compared to that of 99 mTc-TRODAT-1 SPECT (TRODAT). METHODS: A cross-sectional study included PD patients diagnosed in accordance with United Kingdom PD Society Brain Bank criteria and a control group of age and sex- matched healthy subjects. All patients were examined by a movement disorder specialist and underwent brain SPECT using TRODAT, TCS examination and SST-16 test. Receiver Operating Characteristic (ROC) curves were used to calculate cut-off points for TCS, striatal TRODAT binding potentials and SST-16. The area under the ROC curve determined the diagnostic accuracy of the method. RESULTS: Twenty patients with PD (13 males and 7 females) and nine healthy subjects were included. Median age of PD onset was 56.5 years with median disease duration of 5 years. A larger substantia nigra (SN) echogenic area was observed in the PD group (p = 0.013). SN echogenic area cut-off point of 0.22 cm2 was obtained from a ROC curve for PD diagnosis. Considering this cut-off point, TCS diagnostic accuracy was estimated at 79.2% for PD diagnosis. The cut-off value of 0.90 for striatal TRODAT binding was associated with 99% diagnostic accuracy for the diagnosis of PD. SST-16 values equal or less than 9 points showed an 85.8% diagnostic accuracy for PD diagnosis. Combination of both SST-16 and TCS improved the diagnostic accuracy to 95% for PD diagnosis. CONCLUSION: Combined SST-16 and TCS assessment was indicated as accurate for distinguishing PD patients from healthy controls. The diagnostic accuracy of TCS combined with SST-16 for differentiation between idiopathic PD patients and healthy controls is similar to that of SPECT TRODAT.

Evaluation of dopamine transporter density in healthy Brazilians using Tc-99m TRODAT-1 SPECT.

ABSTRACT: The presynaptic dopamine transporter (DAT) modulates the uptake of dopamine by regulating its concentration in the central nervous system. We aimed to evaluate the DAT binding potential (DAT-BP) in a sample of healthy Brazilians through technetium-99 metastable TRODAT-1 single-photon emission computed tomography imaging.We selected 126 healthy individuals comprising 72 men and 54 women, aged 18 to 80 years. We conducted semi-quantitative evaluation in transaxial slices, following which we identified the regions of interest in the striatal region using the occipital lobe as a region of non-specific DAT-BP.We found a decrease in DAT-BP in healthy individuals aged over 30 years, culminating in a 42% mean reduction after 80 years. There was no difference in the decrease by age group between the right (linear regression test [R2] linear = 0.466) and left striatum (R2 linear = 0.510). Women presented a higher DAT-BP than men (women: R2 linear = 0.431; men: R2 linear = 0.457); nonetheless, their decrease by age group was equal to that in men.Our study sheds light on important DAT-BP findings in healthy Brazilian subjects. Our results will facilitate understanding of brain illnesses that involve the dopamine system, such as neuropsychiatric disorders.

Impaired brain dopamine transporter in chemobrain patients submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1.

PURPOSE: "Chemobrain" is a medical secondary effect of cancer chemotherapy treatment characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem-solving skills, and motor function. Dopamine (DA) central nervous system neurotransmitters serve an important role in cognition, and changes in DA could potentially explain impaired cognition associated with chemotherapy. Therefore, our objective was to assess in vivo dopaminergic dysfunction in the central nervous system (CNS) of a group of female breast cancer survivors with cognitive impairment following chemotherapy. METHODS: Twenty-eight women reporting chemobrain were recruited for this study and compared to 22 healthy reference women. Striatal dopamine transporter (DAT) binding ratio was determined by 99mTc-TRODAT-1 (a highly selective radiotracer for DAT in the dorsal striatum) single-photon emission computed tomography and a quantitative evaluation was obtained by DatQUANT™ software (GE Healthcare). The DAT binding ratio (BRDAT) in the patient and control groups was compared using the Student's t test, a multivariate analysis of variance (MANOVA) was used to compare age, years of schooling and BRDAT. The relationship between continuous variables, such as cognitive impairment and BRDAT was assessed using Pearson correlation test. RESULTS: There was a difference in BRDAT between the chemobrain patients and control group. Patients had statistically significant (p < 0.05) lower concentrations of the radiopharmaceutical in the striatum. CONCLUSIONS: We identified a significant dopaminergic decrease in all regions of the dorsal striatum within the patients reporting cognitive dysfunction after chemotherapy. Therefore, our results indicate a possible role of dopamine transporter in the physiopathology of chemobrain, even out of the acute phase of symptoms.

Memory networks in tinnitus: a functional brain image study.

UNLABELLED: Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. The network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. The objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. METHODS: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). The severity of tinnitus was assessed using the "Tinnitus Handicap Inventory" (THI). The images were processed and analyzed using "Statistical Parametric Mapping" (SPM8). RESULTS: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE <0.05) was observed in patients with tinnitus compared with healthy controls. The average total THI score was 50.8+18.24, classified as moderate tinnitus. CONCLUSION: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes.

Substantia nigra echogenicity and imaging of striatal dopamine transporters in Parkinson's disease: a cross-sectional study.

Approximately 10% of patients with a presumed diagnosis of Parkinson's disease (PD) remain misdiagnosed despite recent advances in neuroimaging. The current study addresses the use of transcranial sonography and single-photon emission computed tomography (SPECT) using (99m)Tc-TRODAT-1 to evaluate the echogenicity of the substantia nigra (SN) and the density of striatal presynaptic dopamine transporters, respectively, in a sample of 20 PD patients (13 males and 7 females) and 9 healthy subjects. The median age of the PD patients was 62 years. The median age at disease onset was 56 years, and the median disease duration was 5 years. The SN echogenic area was larger in PD patients than healthy subjects. The cut-off value of 0.22 cm(2) for the SN echogenic area was associated with 100% sensitivity and 78% specificity for the diagnosis of PD. Striatal and putaminal (99m)Tc-TRODAT-1 binding was lower in PD patients than healthy subjects. The cut-off value of 0.90 for the striatal (99m)Tc-TRODAT-1 binding was associated with 100% sensitivity and an 89% specificity for the diagnosis of PD, and the cut-off value of 0.76 for putaminal (99m)Tc-TRODAT-1 binding was associated with an 85% sensitivity and an 89% specificity. The size of the SN echogenic area did not correlate with the degree of striatal (99m)Tc-TRODAT-1 binding in PD patients. In conclusion, both SN hyperechogenicity and decreased striatal or putaminal (99m)Tc-TRODAT-1 binding constitute surrogate markers for differentiating PD patients from healthy individuals with a slightly higher diagnostic specificity of (99m)Tc-TRODAT-1 SPECT.

Dopamine transporter shown by SPECT in patients with periodic leg movement after acute physical exercise.

PURPOSE: This study aimed to evaluate dopamine transporter (DAT) density in patients with periodic leg movement (PLM) shown by [(99mt)Tc]TRODAT-1 single-photon emission computed tomography (SPECT) imaging and to determine the influence of acute physical exercise (maximal exercise test [MET]) on DAT densities. METHODS: Sixteen healthy male volunteers between 45 and 65 yr of age were selected to participate in the study. Each subject (eight subjects in the control group and eight subjects in the patients with PLM experimental group) underwent baseline polysomnography (PSG) to evaluate sleep patterns and PLM index values. After obtaining PSG baselines, SPECT baselines were determined using [(99mt)Tc]TRODAT-1, a selective DAT imaging ligand. Subsequently, the volunteers performed the MET in the morning, followed by a SPECT 2 h later and PSG that night to assess the effect of acute physical exercise on DAT and sleep patterns. RESULTS: The baseline SPECT results showed marginally significantly lower DAT densities in the striatal region of the experimental group. After the MET, no significant differences were observed between groups. The results also showed a significant reduction in the PLM index in the experimental group and a significantly increased percentage of stage 1 non-REM sleep in both groups after MET. CONCLUSIONS: Our results show that patients with PLM had a marginally lower DAT density in the left putamen region compared with the control group. Although the effect of acute physical exercise (MET) reduced PLM symptoms, the results suggest that this improvement was not due to DAT availability.

The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings.

OBJECTIVE: To report structural and functional neuroimaging studies exploring the potential role of the orbitofrontal cortex (OFC) in the pathophysiology of the most prevalent psychiatric disorders (PD). METHOD: A non-systematic literature review was conducted by means of MEDLINE using the following terms as parameters: "orbitofrontal cortex", "schizophrenia", "bipolar disorder", "major depression", "anxiety disorders", "personality disorders" and "drug addiction". The electronic search was done up to July 2011. DISCUSSION: Structural and functional OFC abnormalities have been reported in many PD, namely schizophrenia, mood disorders, anxiety disorders, personality disorders and drug addiction. Structural magnetic resonance imaging studies have reported reduced OFC volume in patients with schizophrenia, mood disorders, PTSD, panic disorder, cluster B personality disorders and drug addiction. Furthermore, functional magnetic resonance imaging studies using cognitive paradigms have shown impaired OFC activity in all PD listed above. CONCLUSION: Neuroimaging studies have observed an important OFC involvement in a number of PD. However, future studies are clearly needed to characterize the specific role of OFC on each PD as well as understanding its role in both normal and pathological behavior, mood regulation and cognitive functioning.

SPEM: a state-of-the-art instrument for high resolution molecular imaging of small animal organs.

OBJECTIVE: To describe the Single Photon Emission Microscope (SPEM), a state-of-the-art instrument for small animal SPECT imaging, and characterize its performance presenting typical images of different animal organs. METHODS: SPEM consists of two independent imaging devices based on high resolution scintillators, high sensitivity and resolution Electron-Multiplying CCDs and multi-pinhole collimators. During image acquisition, the mouse is placed in a rotational vertical holder between the imaging devices. Subsequently, an appropriate software tool based on the Maximum Likelihood algorithm iteratively produces the volumetric image. Radiopharmaceuticals for imaging kidneys, heart, thyroid and brain were used. The mice were injected with 74 to 148 MBq/0,3mL and scanned for 40 to 80 minutes, 30 to 60 minutes afterwards. During this procedure, the animals remained under ketamine/xilazine anesthesia. RESULTS: SPEM images of different mouse organs are presented, attesting the imaging capabilities of the instrument. CONCLUSION: SPEM is an innovative technology for small animal SPECT imaging providing high resolution images with appropriate sensitivity for pre-clinical research. Its use with appropriate radiotracers will allow translational investigation of several animal models of human diseases, their pharmacological treatment and the development of potential new therapeutic agents.

The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings / O envolvimento do cortex orbitofrontal em transtornos psiquiátricos: uma atualização dos achados de neuroimagens

OBJECTIVE: To report structural and functional neuroimaging studies exploring the potential role of the orbitofrontal cortex (OFC) in the pathophysiology of the most prevalent psychiatric disorders (PD). METHOD: A non-systematic literature review was conducted by means of MEDLINE using the following terms as parameters: "orbitofrontal cortex", "schizophrenia", "bipolar disorder", "major depression", "anxiety disorders", "personality disorders" and "drug addiction". The electronic search was done up to July 2011. DISCUSSION: Structural and functional OFC abnormalities have been reported in many PD, namely schizophrenia, mood disorders, anxiety disorders, personality disorders and drug addiction. Structural magnetic resonance imaging studies have reported reduced OFC volume in patients with schizophrenia, mood disorders, PTSD, panic disorder, cluster B personality disorders and drug addiction. Furthermore, functional magnetic resonance imaging studies using cognitive paradigms have shown impaired OFC activity in all PD listed above. CONCLUSION: Neuroimaging studies have observed an important OFC involvement in a number of PD. However, future studies are clearly needed to characterize the specific role of OFC on each PD as well as understanding its role in both normal and pathological behavior, mood regulation and cognitive functioning.

OBJETIVO: Relatar estudos de neuroimagens estruturais e funcionais explorando o papel potencial do córtex orbitofrontal (COF) na fisiopatologia dos transtornos psiquiátricos (TP) mais prevalentes. MÉTODO: Foi realizada uma revisão não sistemática da literatura no MEDLINE, usando como parâmetros os seguintes termos: "córtex orbitofrontal", "esquizofrenia", "transtorno bipolar", "depressão maior", "transtornos ansiosos", "transtornos de personalidade" e "dependência a drogas". A pesquisa eletrônica foi feita até julho de 2011. DISCUSSÃO: Foram relatadas anormalidades estruturais e funcionais do COF em muitos TP, particularmente esquizofrenia, transtornos afetivos, transtornos ansiosos, transtornos de personalidade e dependência a drogas. Estudos de aquisição de imagens estruturais por ressonância magnética relataram a redução do volume do COF em pacientes portadores de esquizofrenia, transtornos afetivos, TEPT, transtorno do pânico, transtornos de personalidade do grupo B e dependência a drogas. Além disso, estudos de aquisição de imagens funcionais por ressonância magnética empregando paradigmas cognitivos demonstraram alterações na atividade do COF em todos os TP anteriormente relacionados. CONCLUSÃO: Estudos de neuroimagens observaram um envolvimento importante do COF em vários TP. Entretanto, estudos futuros são claramente necessários para caracterizar o papel específico do COF em cada TP, assim como para a compreensão de seu papel tanto no comportamento normal como no patológico, na regulação do humor e no funcionamento cognitivo.