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Concept: Single photon emission computed tomography

212

Despite increasing interest in pathological and non-pathological dissociation, few researchers have focused on the spiritual experiences involving dissociative states such as mediumship, in which an individual (the medium) claims to be in communication with, or under the control of, the mind of a deceased person. Our preliminary study investigated psychography - in which allegedly “the spirit writes through the medium’s hand” - for potential associations with specific alterations in cerebral activity. We examined ten healthy psychographers - five less expert mediums and five with substantial experience, ranging from 15 to 47 years of automatic writing and 2 to 18 psychographies per month - using single photon emission computed tomography to scan activity as subjects were writing, in both dissociative trance and non-trance states. The complexity of the original written content they produced was analyzed for each individual and for the sample as a whole. The experienced psychographers showed lower levels of activity in the left culmen, left hippocampus, left inferior occipital gyrus, left anterior cingulate, right superior temporal gyrus and right precentral gyrus during psychography compared to their normal (non-trance) writing. The average complexity scores for psychographed content were higher than those for control writing, for both the whole sample and for experienced mediums. The fact that subjects produced complex content in a trance dissociative state suggests they were not merely relaxed, and relaxation seems an unlikely explanation for the underactivation of brain areas specifically related to the cognitive processing being carried out. This finding deserves further investigation both in terms of replication and explanatory hypotheses.

Concepts: Pseudoscience, Single photon emission computed tomography, Dissociation, Spiritualism, Mediumship, Spiritism, Trance, Cerebrum

195

As neovascularization is essential for tumor growth and metastasis, controlling angiogenesis is a promising tactic in limiting cancer progression. Melatonin has been studied for their inhibitory properties on angiogenesis in cancer. We performed an in vivo study to evaluate the effects of melatonin treatment on angiogenesis in breast cancer. Cell viability was measured by MTT assay after melatonin treatment in triple-negative breast cancer cells (MDA-MB-231). After, cells were implanted in athymic nude mice and treated with melatonin or vehicle daily, administered intraperitoneally 1 hour before turning the room light off. Volume of the tumors was measured weekly with a digital caliper and at the end of treatments animals underwent single photon emission computed tomography (SPECT) with Technetium-99m tagged vascular endothelial growth factor (VEGF) C to detect in vivo angiogenesis. In addition, expression of pro-angiogenic/growth factors in the tumor extracts was evaluated by membrane antibody array and collected tumor tissues were analyzed with histochemical staining. Melatonin in vitro treatment (1 mM) decreased cell viability (p<0.05). The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size and cell proliferation (Ki-67) compared to control animals after 21 days of treatment (p<0.05). Expression of VEGF receptor 2 decreased significantly in the treated animals compared to that of control when determined by immunohistochemistry (p<0.05) but the changes were not significant on SPECT (p>0.05) images. In addition, there was a decrease of micro-vessel density (Von Willebrand Factor) in melatonin treated mice (p<0.05). However, semiquantitative densitometry analysis of membrane array indicated increased expression of epidermal growth factor receptor and insulin-like growth factor 1 in treated tumors compared to vehicle treated tumors (p<0.05). In conclusion, melatonin treatment showed effectiveness in reducing tumor growth and cell proliferation, as well as in the inhibition of angiogenesis.

Concepts: Von Willebrand factor, Oncology, Single photon emission computed tomography, Vascular endothelial growth factor, Growth factor, Metastasis, Breast cancer, Cancer

166

6-Fluoro-((18)F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, (123)I-metaiodobenzylguanidine (MIBG) and (111)In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for (123)I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as small cell prostate cancer, or in emerging indications, such as metastatic NET of unknown primary (CUP-NET) or adrenocorticotropic hormone (ACTH) ectopic production. An evidence-based strategy in NET functional imaging is as yet affected by a low number of comparative studies. Then the suggested diagnostic trees, being a consequence of the analysis of present data, could be modified, for some indications, by a wider experience mainly involving face-to-face studies comparing FDOPA and (68)Ga-labelled peptides.

Concepts: Nuclear medicine, Neuroimaging, Carcinoid, Cancer, Medical imaging, Single photon emission computed tomography, Oncology, Positron emission tomography

29

Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimer’s disease. We have developed a novel PHF-tau targeting positron emission tomography imaging agent, [F-18]-T807, which may be useful for imaging Alzheimer’s disease and other tauopathies. Here, we describe the first human brain images with [F-18]-T807.

Concepts: Single photon emission computed tomography, Fluorine-18, Neurofibrillary tangle, Carbon-11, Positron, Neuroimaging, Alzheimer's disease, Positron emission tomography

28

OBJECTIVE: The objective of this study was to identify specific brain lesions with regional perfusion abnormalities possibly associated with neuropsychological impairments (NPI), as sequela after mild traumatic brain injury (MTBI), using 99mTc-ethylcysteinate dimer single photon emission computed tomography (Tc-99m ECD SPECT) and its novel analytic software. METHODS: We studied 23 patients with diffuse axonal injury with NPI group (Impaired-DAI), 26 with MTBI with NPI group (Impaired-MTBI) and 24 with MTBI without NPI group (Healthy-MTBI). In each subject, Tc-99m ECD SPECT images were analyzed by easy Z score imaging system (eZIS) and voxel-based stereotactic extraction estimation (vbSEE). Segmented into lobule levels, ROIs were set in 140 areas in whole brain, and relative regional low Tc-99m ECD uptake was computed as “extent” (rate of coordinates with Z score >2.0 in the ROI). Receiver operating characteristic analysis was performed using “extent” to discriminate the three groups. RESULTS: The highest area under the curve (AUC) value for data of Impaired-DAI and Healthy-MTBI groups was obtained in ROI on the left anterior cingulate gyrus (LtACG), with AUC of 0.93, optimal “extent” cutoff value of 10.9 %, sensitivity 87.0 %, specificity 83.3 %. The highest AUC value for data of Impaired-MTBI and Healthy-MTBI groups was also in the LtACG, with AUC of 0.87, optimal “extent” cutoff value of 9.2 %, sensitivity 73.1 %, specificity 83.3 %. CONCLUSIONS: Using two analytic software packages, eZIS and vbSEE, we identified specific lesions with low regional Tc-99m ECD uptake possibly associated with NPIs after MTBI. Especially, this trend was most marked in the left anterior cingulate gyrus in MTBI patients with NPIs and those with DAI. The optimal “extent” cutoff value, as a criterion for SPECT abnormality, might help the diagnosis of NPIs after MTBI.

Concepts: Concussion, Brodmann area 24, Medical imaging, Cerebrum, Cingulate gyrus, Diffuse axonal injury, Traumatic brain injury, Single photon emission computed tomography

28

Differences in the performance of cadmium-zinc-telluride (CZT) cameras or collimation systems that have recently been commercialized for myocardial SPECT remain unclear. In the present study, the performance of 3 of these systems was compared by a comprehensive analysis of phantom and human SPECT images. METHODS: We evaluated the Discovery NM 530c and DSPECT CZT cameras, as well as the Symbia Anger camera equipped with an astigmatic (IQ⋅SPECT) or parallel-hole (conventional SPECT) collimator. Physical performance was compared on reconstructed SPECT images from a phantom and from comparable groups of healthy subjects. RESULTS: Classifications were as follows, in order of performance. For count sensitivity on cardiac phantom images (counts⋅s(-1)⋅MBq(-1)), DSPECT had a sensitivity of 850; Discovery NM 530c, 460; IQ⋅SPECT, 390; and conventional SPECT, 130. This classification was similar to that of myocardial counts normalized to injected activities from human images (respective mean values, in counts⋅s(-1)⋅MBq(-1): 11.4 ± 2.6, 5.6 ± 1.4, 2.7 ± 0.7, and 0.6 ± 0.1). For central spatial resolution: Discovery NM 530c was 6.7 mm; DSPECT, 8.6 mm; IQ⋅SPECT, 15.0 mm; and conventional SPECT, 15.3 mm, also in accordance with the analysis of the sharpness of myocardial contours on human images (in cm(-1): 1.02 ± 0.17, 0.92 ± 0.11, 0.64 ± 0.12, and 0.65 ± 0.06, respectively). For contrast-to-noise ratio on the phantom: Discovery NM 530c had a ratio of 4.6; DSPECT, 4.1; IQ⋅SPECT, 3.9; and conventional SPECT, 3.5, similar to ratios documented on human images (5.2 ± 1.0, 4.5 ± 0.5, 3.9 ± 0.6, and 3.4 ± 0.3, respectively). CONCLUSION: The performance of CZT cameras is dramatically higher than that of Anger cameras, even for human SPECT images. However, CZT cameras differ in that spatial resolution and contrast-to-noise ratio are better with the Discovery NM 530c, whereas count sensitivity is markedly higher with the DSPECT.

Concepts: Ratios, Count, Collimator, Radiology, Single photon emission computed tomography, Ratio, Phantom, Optics

27

Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct.

Concepts: Stress, Posttraumatic stress disorder, Functional neuroimaging, Psychological trauma, Neuroimaging, Medical imaging, Traumatic brain injury, Single photon emission computed tomography

27

In single-photon emission computed tomography (SPECT), multi-pinhole collimation is often employed nowadays. Most multi-pinhole collimators avoid overlap (multiplexing) of the projections on the detector. This can be done by using additional shielding or by spacing the pinholes far enough apart. Using additional shielding has the drawback that it increases weight, design complexity and cost. Spacing the pinholes far enough apart results in sub-optimal detector usage, the valuable detector area is not entirely used. This is due to the circular projections of pinholes on the detector; these ellipses can not be tiled with high detector coverage. To overcome this we designed a new pinhole geometry, the lofthole, that has a rectangular projection on the detector. The lofthole has a circular aperture and a rectangular entrance/exit opening. Sensitivity formulae have been derived for pinholes and loftholes. These formulae take the penumbra effect into account; the proposed formulae do not take penetration into account. The derived formulae are valid for geometries where the field-of-view and the sensitivity of the aperture are solely limited by the exit window. A flood map measurement was performed to compare the rectangular projection of a lofthole with the circular projection of a pinhole. Finally, measurements were done to compare the amount of penetration of pinholes with the amount of penetration of a lofthole. A square lofthole collimator has less penetration than a knife-edge pinhole collimator that irradiates the same rectangular detector area with full coverage. A multi-lofthole collimator allows high detector coverage without using additional shielding. An additional advantage is the lower amount of penetration.

Concepts: Pinhole camera, Projection, Area, Single photon emission computed tomography, Square, Medical imaging, Collimator, Map projection

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AIM: The aim of our study was to assess improvements in spatial resolution and noise control from the application of the Astonish resolution recovery algorithm for single photon emission computed tomography imaging. Secondary aims were to compare acquisitions made with low-energy general purpose collimators with those obtained using low-energy high-resolution collimators in this context and evaluate the potential of a finer matrix to improve image quality further. MATERIALS AND METHODS: A Tc-filled Jaszczak phantom with hot spheres was used to assess contrast and noise. A National Electrical Manufacturers Association triple line source single photon emission computed tomography resolution phantom was used to measure spatial resolution. Acquisitions were made using both low-energy high-resolution and low-energy general purpose collimators. RESULTS: Compared with standard ordered subsets expectation maximization reconstructions, the resolution recovery algorithm resulted in a higher spatial resolution (8 vs. 14 mm full-width at half-maximum) leading to reduced partial volume effects in the smaller Jaszczak spheres. Higher image contrast was achieved alongside lower levels of noise. An edge enhancement artefact was observed in the resolution recovery corrected images. An overestimate of the target-to-background activity was also observed for the larger spheres. CONCLUSION: The use of such an algorithm results in images characterized by increased spatial resolution and reduced noise. However, small sources of the order of 2-3 cm can be significantly overenhanced.

Concepts: Reconstruction algorithm, IMAGE, National Electrical Manufacturers Association, Tomography, Estimation theory, Single photon emission computed tomography, Medical imaging, Optics

26

Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson’s disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson’s disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson’s Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson’s disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson’s disease, 185 healthy controls, and 56 subjects with possible Parkinson’s disease without evidence of dopaminergic deficit were included. In the Parkinson’s disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson’s disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous Parkinson's disease subgroup had significantly lower raphe serotonin transporter availability but less severe striatal dopaminergic deficits compared to akinetic-rigid patients with no resting tremor (P < 0.05). In tremulous patients, raphe serotonin transporter availability was also associated with rest tremor constancy (β = -0.380, P < 0.05) and index of rest tremor severity (β = -0.322, P < 0.05). There was no association between raphe serotonin transporter availability and fatigue, depression, excessive daytime sleepiness, or rapid eye movement sleep behaviour disorder in early Parkinson's disease. We conclude that the raphe nuclei are affected in a subgroup of early drug-naïve Parkinson's disease patients and that reduced raphe serotonin transporter availability is associated with the severity of resting tremor but not non-motor symptoms.

Concepts: Raphe nuclei, Antipsychotic, Single photon emission computed tomography, Haloperidol, Dopamine, Tremor, Parkinson's disease, Serotonin