David Towey

Clinical correlates of raphe serotonergic dysfunction in early Parkinson’s disease

Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinsons 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 Parkinsons 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 Parkinsons Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinsons 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 Parkinsons disease, 185 healthy controls, and 56 subjects with possible Parkinsons disease without evidence of dopaminergic deficit were included. In the Parkinsons disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinsons 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 Parkinsons disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinsons 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 Parkinsons 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 Parkinsons disease. We conclude that the raphe nuclei are affected in a subgroup of early drug-naïve Parkinsons disease patients and that reduced raphe serotonin transporter availability is associated with the severity of resting tremor but not non-motor symptoms.

68Ga-DOTATATE PET in neuroectodermal tumours: first experience.

Background and aimPhaeochromocytoma is initially imaged with computed tomography (CT) or magnetic resonance imaging (MRI) but functional imaging is commonly needed to assess disease activity, the presence of metastasis and response to therapy. Traditionally, this is done with 123I -MIBG with good sensitivity and specificity. However, spatial resolution remains limited even with SPECT. We aimed to assess the utility of a new somatostatin analogue PET tracer, 68Ga-DOTATATE in the management of phaeochromocytoma. MethodsWe retrospectively reviewed five patients with malignant phaeochromocytoma who underwent imaging with CT and 123I-MIBG and compared the results with those of PET imaging using 68Ga-DOTATATE. Blinded analysis of the numbers and extent of lesions were done for all imaging modality. ResultsTwo patients had negative 123I-MIBG and positive 68Ga-DOTATATE scans. One had a weakly positive 123I-MIBG and a strongly positive 68Ga-DOTATATE scan. One had a positive 123I-MIBG and positive 68Ga-DOTATATE scans. The fifth patient was negative to all imaging including CT. 68Ga-DOTATATE showed more lesions with higher uptake and better resolution compared to 123I-MIBG. ConclusionThe findings in our small group of patients demonstrate the value of somatostatin receptor PET imaging in malignant phaeochromocytoma. In lesions with no or low MIBG uptake, the next investigation of choice should be PET imaging with 68Ga-DOTATATE, in view to therapy with 90Y-labelled DOTATATE.

Automatic classification of 123I-FP-CIT (DaTSCAN) SPECT images.

IntroductionWe present a method of automatic classification of 123I-fluoropropyl-carbomethoxy-3&bgr;-4-iodophenyltropane (FP-CIT) images. This technique uses singular value decomposition (SVD) to reduce a training set of patient image data into vectors in feature space (D space). The automatic classification techniques use the distribution of the training data in D space to define classification boundaries. Subsequent patients can be mapped into D space, and their classification can be automatically given. MethodsThe technique has been tested using 116 patients for whom the diagnosis of either Parkinsonian syndrome or non-Parkinsonian syndrome has been confirmed from post 123I-FP-CIT imaging follow-up. The first three components were used to define D space. Two automatic classification tools were used, naïve Bayes (NB) and group prototype. A leave-one-out cross-validation was performed to repeatedly train and test the automatic classification system. Four commercially available systems for the classification were tested using the same clinical database. ResultsThe proposed technique combining SVD and NB correctly classified 110 of 116 patients (94.8%), with a sensitivity of 93.7% and specificity of 97.3%. The combination of SVD and an automatic classifier performed as well or better than the commercially available systems. ConclusionThe combination of data reduction by SVD with automatic classifiers such as NB can provide good diagnostic accuracy and may be a useful adjunct to clinical reporting.

An audit of half-count myocardial perfusion imaging using resolution recovery software.

IntroductionThe Nuclear Medicine Software Quality Group of the Institute of Physics and Engineering in Medicine has conducted a multicentre, multivendor audit to evaluate the use of resolution recovery software from several manufacturers when applied to myocardial perfusion data with half the normal counts acquired under a variety of clinical protocols in a range of departments. The objective was to determine whether centres could obtain clinical results with half-count data processed with resolution recovery software that were equivalent to those obtained using their normal protocols. Materials and methodsSixteen centres selected 50 routine myocardial perfusion studies each, from which the Nuclear Medicine Software Quality Group generated simulated half-count studies using Poisson resampling. These half-count studies were reconstructed using resolution recovery and the clinical reports compared with the original reports from the full-count data. A total of 769 patient studies were processed and compared. ResultsEight centres found only a small number of clinically relevant discrepancies between the two reports, whereas eight had an unacceptably high number of discrepancies. There were no significant differences in acquisition parameters between the two groups, although centres finding a high number of discrepancies were more likely to perform both rest and stress scans on normal studies. ConclusionHalf of the participating centres could potentially make use of resolution recovery to reduce the administered activity for myocardial perfusion scans without changing their routine acquisition protocols. The other half could consider adjusting the reconstruction parameters used with their resolution recovery software if they wish to use reduced activity successfully.

UK audit of quantitative thyroid uptake imaging

Aim A national audit of quantitative thyroid uptake imaging was conducted by the Nuclear Medicine Software Quality Group of the Institute of Physics and Engineering in Medicine in 2014/2015. The aims of the audit were to measure and assess the variability in thyroid uptake results across the UK and to compare local protocols with British Nuclear Medicine Society (BNMS) guidelines. Participants and methods Participants were invited through a combination of emails on a public mailbase and targeted invitations from regional co-ordinators. All participants were given a set of images from which to calculate quantitative measures and a spreadsheet for capturing results. The image data consisted of two sets of 10 anterior thyroid images, half of which were acquired after administration of 99mTc-pertechnetate and the other half after administration of 123I-iodide. Images of the administration syringes or thyroid phantoms were also included. Results In total, 54 participants responded to the audit. The median number of scans conducted per year was 50. A majority of centres had at least one noncompliance in comparison with BNMS guidelines. Of most concern was the widespread lack of injection-site imaging. Quantitative results showed that both intersite and intrasite variability were low for the 99mTc dataset. The coefficient of quartile deviation was between 0.03 and 0.13 for measurements of overall percentage uptake. Although the number of returns for the 123I dataset was smaller, the level of variability between participants was greater (the coefficient of quartile deviation was between 0.17 and 0.25). Conclusion A UK-wide audit showed that thyroid uptake imaging is still a common test in the UK. It was found that most centres do not adhere to all aspects of the BNMS practice guidelines but that quantitative results are reasonably consistent for 99mTc-based scans.

PO105 Levodopa-induced dyskinesias in parkinson’s: imaging of striatal dat density over time

Background/Aim The density of the dopamine transporter (DAT) continues to decline in the striatum of Parkinson’s disease (PD) patients, while they get at risk for developing levodopa-induced dyskinesias (LIDs). Here, we studied the role of DAT-specific imaging as a prognostic marker of dyskinesias. Methods We retrospectively selected 42 PD patients who had SPECT imaging with 123I-Ioflupane approximately five years ago during the diagnosis of PD. 15 patients of them were rescanned with 123I-Ioflupane SPECT after 6.3±3.0 years. We divided the PD patients according to the presence or absence of dyskinesias. SPECT data were analysed for the putamen by a semi-quantification approach. Results 10 PD patients had developed LIDs, while 32 were non-dyskinetic. The putaminal mean 123I-Ioflupane uptake in the LIDs (1.7±0.4) group was not statistically different as compared to the non-LIDs group (1.7±0.5;p>010). All 15 PD patients who had a second SPECT scan showed significant reductions in the putaminal 123I-Iofluplane uptake (p<0.001) as compared to their first scan. Within this subgroup, the LIDs (n=8) had significantly lower DAT uptake (1.1±0.3) as compared to the non-LIDs patients (n=7); (1.5±0.5; p<0.05). Conclusion 123I-Ioflupane SPECT imaging in de novo PD, cannot predict the onset of LIDs within five years from diagnosis. As shown in the group that repeated 123I-Ioflupane SPECT imaging, the onset of LIDs may be linked to a faster decline of putaminal DAT availability.

SEROTONIN-TO-DOPAMINE TRANSPORTER RATIOS IN THE STRIATUM OF PATIENTS WITH PARKINSON'S DISEASE: IMPACT ON LEVODOPA–INDUCED DYSKINESIAS

Background Serotonergic mechanisms play a key role in the development of the Levodopa-induced dyskinesias (LIDs) in patients with Parkinsons disease (PD). We hypothesised that an unfavourable serotonin-to-dopamine terminal ratio in the putamen would be most detrimental in dyskinetic patients. We investigated the role of serotonin-to-dopamine transporter binding ratios in the development of dyskinesias in Parkinsons disease patients. Methods/Subjects Twenty-eight Parkinsons disease patients[17 with LIDs;11 stable] and 12 age and gender-matched healthy controls were studied with [11C]DASB PET and [123I]FP-CIT SPECT, Imaging. We have employed a simplified reference tissue model using cerebellar reference for the quantification of [11C]DASB, whereas a semi-quantification approach was used for [123I]FP-CIT. We estimated uptake values in the putamen. Results Parkinsons disease patients showed decreases in [123I]FP-CIT binding (p<0.001) compared to controls, 51% in the stable and 62% in the LIDs group. PD patients showed decreases in [11C]DASB binding (p<0.01), but there were no differences between the stable (37% loss) and LIDs(31% loss) groups. PD patients with LIDs had 103% increased [11C]DASB-to-[123I]FP-CIT binding ratio, whereas in the PD stable group the ratio was increased by 76%, relative to HCs. Higher [11C]DASB-to-[123I]FP-CIT binding ratio correlated with longer disease duration for the 28 PD patients (r=0.52;p<0.01). Conclusion SERT-to-DAT ratio increases as PD progresses and patients experience LIDs.

British Nuclear Medicine Society 42nd Annual Meeting Harrogate 11–14 May 2014: 1 UK audit of glomerular filtration rate measurement in 2013

1 UK audit of glomerular filtration rate measurement in 2013 A. Murray, R. Lawson, S. Cade, D. Hall, B. Kenny, E. O’Shaughnessy, J. Taylor, D. Towey and D. White University of Cumbria, Lancaster, Central Manchester University Hospitals NHS Foundation Trust, Manchester, Royal United Hospital Bath NHS Trust, Bath, University Hospitals Bristol NHS Foundation Trust, Bristol, Link Medical, Bramshill, Poole Hospital NHS Foundation Trust, Dorset, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, Imperial College Healthcare NHS Trust, London and Barnsley Hospital NHS Foundation Trust, Barnsley, UK