Interictal SPECT is a critical component of SISCOM analysis for presurgical localisation of epileptogenic regions. However, its clinical reliability can be affected by uncertainty regarding whether the interictal scan is a true representation of a seizure free baseline (i.e., the interictal state). In addition, most patients will also have an interictal FDG PET scan and MRI performed, and it would be useful if the number of scans required could be reduced. This study explores the use of machine learning synthesised interictal SPECT within the SISCOM framework (i.e., SySCOM) as an alternative baseline to the acquired interictal SPECT scan. PET scans from 40 patients with refractory focal epilepsy were used to train a three-dimensional generative adversarial network to synthesise interictal SPECT images. Synthesis performance was evaluated on an independent validation cohort of nine unseen patients using standard image quality metrics (i.e., SSIM, PSNR, RMSE). Both real and synthetic interictal SPECT images were used to generate SISCOM outputs following standard clinical protocols. Five clinicians experienced in the interpretation of SPECT images in epilepsy performed blinded visual localisation of regions of hyperperfusion across 18 predefined anatomical regions. Observer based similarity, agreement, and reproducibility between SISCOM and SySCOM were assessed. Synthetic interictal SPECT images demonstrated high similarity to real images (mean SSIM = 0.94, mean PSNR = 27.9 dB, mean RMSE = 0.041). Visual localisation based comparison of SISCOM with SySCOM demonstrated good agreement between the methods (Dice score = 70

BackgroundCross-modality image estimation can be performed using generative adversarial networks (GANs). To date, SPECT image estimation from another medical imaging modality using this technique has not been considered. We evaluate the estimation of SPECT from MRI and PET, and additionally assess the necessity for cross-modality image registration for GAN training.MethodsWe estimated interictal SPECT from PET and MRI as a single-channel input, and as a multi-channel input to the GAN. We collected data from 48 individuals with epilepsy and converted them to 3D isotropic images for consistence across the modalities. Training and testing data were prepared in native and template spaces. The Pix2pix framework within the GAN network was adopted. We evaluated the addition of the structural similarity index metric to the loss function in the GAN implementation. Root-mean-square error, structural similarity index, and peak signal-to-noise ratio were used to assess how well SPECT images were able to be synthesised.ResultsHigh quality SPECT images could be synthesised in each case. On average, the use of native space images resulted in a 5.4% percentage improvement in SSIM than the use of images registered to template space. The addition of structural similarity index metric to the GAN loss function did not result in improved synthetic SPECT images. Using PET in either the single channel or dual channel implementation led to the best results, however MRI could produce SPECT images close in quality.ConclusionSynthesis of SPECT from MRI or PET can potentially reduce the number of scans needed for epilepsy patient evaluation and reduce patient exposure to radiation.

BACKGROUND:Cardiac metastases from neuroendocrine neoplasms (NENs) are being detected with increasing frequency, although the optimal imaging strategy remains unclear. We performed a single-center retrospective study to explore the role of somatostatin receptor positron emission tomography/computed tomography (SSTR PET/CT) and cardiac magnetic resonance imaging (CMR) in NEN cardiac metastases, determine the degree of concordance between the findings of these imaging modalities, and examine the advantages and disadvantages of each imaging technique. A secondary aim was to determine if cardiac metastases were associated with adverse cardiac events during peptide receptor radionuclide therapy (PRRT). METHODS AND RESULTS:19 patients with NEN cardiac metastases were identified. A retrospective review of electronic medical records was performed, and if available SSTR PET/CT and CMR were blindly re-reviewed by imaging specialists, documenting the number and location of cardiac metastases. All 19 patients had SSTR PET/CT, and 10/19 patients had CMR. SSTR PET/CT identified more metastases than CMR. When identified on CMR, metastases were more accurately localized. 12/19 patients received PRRT, with no cardiac adverse effects. CONCLUSION:SSTR PET/CT and CMR are complementary investigations in the imaging of NEN cardiac metastases. SSTR PET/CT appears more sensitive for lesion detection, and CMR offers better lesion characterization. Both investigations present useful information for the planning of treatment including PRRT, which was administered safely.

The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending 18F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using 18F-FDG uptake as a surrogate marker. A retrospective audit was conducted of the brain 18F-FDG uptake in 52 patients who underwent PET scans for possible cardiac sarcoidosis or suspected intracardiac infection, following a ketogenic diet and prolonged fasting. SUVbw for whole brain and separate brain regions was compared with serum glucose and serum ketone body (beta-hydroxybutyrate) levels. The expected negative association between serum glucose levels and whole brain 18F-FDG uptake was confirmed. A reduction in SUVbw due to increasing serum ketones levels was also observed that was independent of and in addition to the effects of glucose. The magnitude of the reduction in SUVbw related to serum glucose level and serum ketone level was found to be greater in the precuneus than in the cerebellum or whole brain. In a real-world clinical PET setting, cerebral 18F-FDG uptake appears to be affected by glycaemia and ketonaemia. This means when assessing the brain, both serum glucose and ketone levels need to be considered when SUVs are used to distinguish between pathologic and physiologic states. The magnitude of this effect appears to vary between different brain regions. This regional difference should be taken into consideration when selecting the appropriate brain region for SUV normalisation, particularly when undertaking database comparison in the assessment of dementia.

e16198 Background: There is relatively limited data guiding optimal treatment algorithms for inoperable or metastatic neuroendocrine tumours (NETs). The randomised NETTER 1 study established PRRT as a standard of care in midgut NET. The aim of this study was to retrospectively review the efficacy and safety of patients treated with 177Lu-DOTATATE at Royal Brisbane and Women’s Hospital. Methods: Consecutive patients with unresectable or metastatic NET who received their first 177Lu-DOTATATE therapy between 2010 and 2017 were identified. Paragangliomas were excluded. Response rates, progression free survival (PFS) and overall survival (OS) were assessed via a combination of chart review, post-therapeutic 68Ga DOTATATE PET/CT and multi-disciplinary meeting decisions. Gr3/4 haematological and renal safety data was analysed via chart review. Progression free survival (PFS) and overall survival (OS) were assessed via the Kaplan-Meier method. Results: 123 consecutive patients were included in the analysis (57% male, median age 61). Primary site: 41% gastroenteric, 34% pancreatic, 10% lung, 6% colon/rectum, 9% other. Grade 1 (42%), Grade 2 (31%) Grade 3 (6%), unknown (21%). 76% of patients had previously received somatostatin analogues. 80% received four cycles (with persistent myelosuppression the most common cause of ceasing therapy early). 20% of patients received concurrent chemotherapy (10% capecitabine, 10% capecitabine and temozolomide). For the entire cohort, median follow up was 51 months. Median PFS, 34.2 months (95% CI, 30.3 – 38.17) and median OS, 61 months (95% CI, 54.2– 67.8). There was no significant difference in PFS or OS between small bowel and pancreatic patients. Response rates to PRRT included complete response (n = 4, 3%), stable or responding disease (n = 96, 78%), progressive disease (n = 22, 18%), not assessable (1, 1%). Grade 3 or 4 thrombocytopenia, neutropenia or anaemia occurred in less than 1% of patients. Confirmed acute leukaemia occurred in three patients. One patient had grade 3 renal toxicity secondary to treatment. 26 patients received retreatment with 177Lu-DOTATATE at progression with median time to re-treatment of 35 months. Conclusions: This single centre, retrospective audit confirms the efficacy of 177Lu-DOTATATE in the treatment of unresectable and metastatic NETs. Treatment was associated with low rates of severe haematological or renal adverse events. Our results are comparable to similar published reviews.

Nuclear medicine bone scans differentiate ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders, helping to make the diagnosis without biopsy. Standard bone scans are not absolutely quantitative, so are assessed by comparing the heart to other tissues. The standard visual scoring system compares heart to bone. This accurately diagnoses ATTR-CM and has been validated in a multicenter study, but has limitations. Semiquantitative techniques including heart/contralateral thorax (H/CL) and heart/whole body ratio (H/WB) improve on visual scoring but still rely on extracardiac sites as comparators. Absolute quantitation of myocardial uptake using quantitative SPECT should help overcome these shortcomings. In ATTR-CM, this technique is practical, accurately makes the diagnosis and provides information that is not identical to visual scores. However, more work needs to be done. The reproducibility in ATTR-CM must be tested. Larger studies need to be undertaken to determine whether quantitative SPECT measurements can assess prognosis, disease progression or treatment response. As ATTR-CM is relatively uncommon multicenter trials will help recruit enough subjects to answer these questions. Accurate measurement techniques are needed in ATTR-CM to enable appropriate use of proven therapy and to conduct trials of new therapeutic agents. Quantitative bone scans offer a promising avenue.

Nuclear medicine bone scans differentiate ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders, helping to make the diagnosis without biopsy. Standard bone scans are not absolutely quantitative, so are assessed by comparing the heart to other tissues. The standard visual scoring system compares heart to bone. This accurately diagnoses ATTR-CM and has been validated in a multicenter study, but has limitations. Semiquantitative techniques including heart/contralateral thorax (H/CL) and heart/whole body ratio (H/WB) improve on visual scoring but still rely on extracardiac sites as comparators. Absolute quantitation of myocardial uptake using quantitative SPECT should help overcome these shortcomings. In ATTR-CM, this technique is practical, accurately makes the diagnosis and provides information that is not identical to visual scores. However, more work needs to be done. The reproducibility in ATTR-CM must be tested. Larger studies need to be undertaken to determine whether quantitative SPECT measurements can assess prognosis, disease progression or treatment response. As ATTR-CM is relatively uncommon multicenter trials will help recruit enough subjects to answer these questions. Accurate measurement techniques are needed in ATTR-CM to enable appropriate use of proven therapy and to conduct trials of new therapeutic agents. Quantitative bone scans offer a promising avenue.

Background99mTechnetium-HDP (HDP) bone scans differentiate transthyretin (ATTR) cardiac amyloid from other infiltrative myocardial diseases. These scans are not quantitative and are assessed by comparing myocardial uptake to bone. This study examined whether quantitative HDP SPECT/CT can discriminate individuals with cardiac ATTR from the population without this disease.MethodsHDP thoracic xSPECT/CT QUANT (xQUANT) was performed in 29 patients: ATTR cardiac amyloid (n=6); AL cardiac amyloid (n=1); other infiltrative myocardial disease (n=4); no known infiltrative cardiac disease (n=18). SUVmax measured within volumes of interest for whole heart, ascending aorta blood pool, and specific bones. HDP myocardial uptake calculated as whole heart minus blood pool.ResultsThe cardiac ATTR group had greater HDP myocardial uptake than those with no known infiltrative disease (p=0.002). AL and other myocardial diseases had uptake indistinguishable from the group with no known infiltrative cardiac disease. The SUVmaxima were sufficiently similar between individuals without cardiac ATTR that a 99% reference interval for HDP uptake could be calculated, providing an upper limit cut point of SUVmax 1.2. Individuals with cardiac ATTR had SUVmax well above this cut point.ConclusionQuantitative SPECT/CT can measure HDP myocardial uptake in individuals with normal hearts and those with cardiac ATTR without recourse to comparison with bone. It enables calculation of a reference interval for HDP myocardial uptake in the population without ATTR cardiac amyloid. Using this reference interval single individuals with cardiac ATTR can be accurately discriminated from the non-affected population. This technique uses a NIST traceable calibration source, potentially allowing development of multicentre clinical decision limits. Its role in disease management warrants further assessment.

We present a case of Ga-68-PSMA PET/CT imaging of PSMA expression in neurofibromas in a patient with neurofibromatosis type 1 (or von Recklinghausen disease). PSMA uptake has previously been demonstrated in schwannomas both with PET and histological staining. The presented images confirm that PSMA expression in cutaneous neurofibromas can be well imaged with PET, with uptake mostly at relatively low levels. Interestingly, some lesions demonstrated significantly higher PSMA expression, although the clinical significance of these differences remains to be determined. The images raise the possibility of a potential role for Ga-68-PSMA PET/CT in neurofibromatosis type 1 monitoring.

Synchrotron-based X-ray fluorescence microscopy (XFM) can localise chemical elements at a subcellular level. 99mTechnetium stannous (TcSn) colloid is taken up by phagocytes via a Complement Receptor 3 mediated phagocytic process. In the current study, XFM was used to examine the intracellular trafficking of TcSn colloid in neutrophils. XFM was performed on TcSn colloid, and neutrophils labelled with TcSn colloid, in whole blood. We developed a set of pixel by pixel analysis and mapping techniques incorporating cluster analysis that allowed us to differentiate neutrophils and artefactual contaminants, and we examined the changes in element distribution that accompany neutrophil phagocytosis of TcSn colloid. Sn became associated with half the neutrophils. Within cells, Sn colocalised with iron (Fe) and sulphur (S), and was negatively associated with calcium (Ca). Despite the high sensitivity of XFM, Tc was not detected. XFM can help clarify the intracellular processes that accompany neutrophil phagocytosis. The subcellular colocalisation of Sn with Fe is consistent with fusion of the colloid-containing phagosome with neutrophil granules. The association of Sn with S suggests that proteins rich in S-containing amino acids are present in the phagosome. The negative colocalisation with Ca indicates that ongoing maturation of the TcSn colloid phagosome is no longer calcium dependent one hour after phagocytosis.

UNLABELLED:INTRODUCTION (PURPOSE OF THE STUDY): The objective of this study was to assess whether dual-time-point (18)F-fluoro-2-deoxyglucose ((18)F-FDG)-PET/CT imaging improved the evaluation of suspected malignancy and if there was any resulting change in management. METHODS:A total of 53 patients with suspected malignancy were investigated by performing two static acquisitions started at mean times t = 64 and t = 155 min after the tracer injection. The total number of malignant lesions was 133 and the total number of benign lesions was 61. Visual and semiquantitative analysis was performed on both the early and delayed images. RESULTS:Overall, there was a significant improvement (P < 0.001) in the sensitivity of delayed imaging (94%) compared with early imaging (77%) in detecting malignant lesions, without a reduction in specificity. In 10 patients, 13 malignant lesions were undetected on early imaging alone but detected on delayed imaging. In seven patients, 10 malignant lesions were incorrectly classified as 'likely benign' on early imaging but correctly reported as 'likely malignant' on delayed imaging. Management was altered in 2 out of 17 patients. Overall, delayed imaging altered management in 2 out of 53 studied patients. Dual-time-point (18)FDG-PET/CT imaging was useful in differentiating malignant from benign intra-abdominal lesions but did not improve the evaluation of pulmonary lesions. CONCLUSIONS:(18)F-FDG-PET/CT imaging should be performed as late as reasonably possible after tracer administration in order to increase tumour-to-background contrast and thereby improve the sensitivity of demonstrating additional sites of disease. Dual-time-point (18)FDG-PET/CT may be of benefit in the evaluation of intra-abdominal lesions but does not improve the overall evaluation of pulmonary lesions.

Neutrophil granulocytes (neutrophils) play a central role in the innate immune response to Gram negative bacterial infection. In this chapter we discuss the immune response generated in response to Burkholderia pseudomallei, the causative agent of the tropical infection melioidosis. In more detail we examine changes that occur in the phagocytic function of human neutrophils in response to this infection, concentrating on work performed in our unit.Neutrophils and monocytes/macrophages internalise particulate matter by phagocytosis. In the 1950's it was recognised that phagocytosis could be assessed by measuring cellular uptake of radioactive inorganic colloids. Susequent clarification of underlying cellular mechanisms has allowed a better understanding of what radiocolloid uptake techniques can tell us about phagocytic function.[99mTc]technetium stannous colloid (TcSnC) labels neutrophils and monocytes by phagocytosis. Labelled cells accumulate at inflammatory foci, enabling Nuclear Medicine imaging of these sites. We have established the clinical usefulness of this technique in melioidosis. During these studies we found neutrophil TcSnC uptake was reduced in melioidosis. It was also reduced when whole blood from healthy volunteers was exposed to B pseudomallei cell products in the absence of live bacteria. This counterintuitive result, that infection with B pseudomallei is associated with reduced neutrophil phagocytosis, may well have pathophysiological significance. This concept is supported by reports that G-CSF treatment can improve prognosis in patients with severe melioidosis. However treatment response is variable. It is possible it could be more effective if targeted at individuals with proven neutrophil phagocytic dysfunction.These results led us to examine the mechanisms underlying neutrophil TcSnC uptake and effects of bacterial products on this process. We found that neutrophil TcSnC uptake is mediated by Complement Receptor 3 (CR3), a receptor central to phagocytosis and neutrophil migration. Furthermore we confirmed that neutrophils which have taken up TcSnC are not activated, nor are they significantly primed. However their response to a priming stimulus (low dose LPS) is increased. This indicates that TcSnC uptake is not mediated by other phagocytic receptors (such as FcR) that activate cells.Reduced neutrophil TcSnC uptake in melioidosis therefore suggests alteration in CR3 function in this infection. We have attempted to identify the causative bacterial factors. LPS has a similar effect on TcSnC uptake. Other B pseudomallei virulence factors (eg rhamnolipids, proteinaceous compounds) may also affect neutrophil function, and we have identified one potential causative protein. TNF alpha and GM-CSF have an effect on TcSnC uptake similar to LPS, while G-CSF and IFN-gamma alone do not. In addition our observations indicate that CR3 function is affected by gender and oestrogen levels. Further investigation of these relationships is warranted.We have developed a relatively simple quantitative functional test of CR3 related phagocytosis that can be performed in whole blood, avoiding changes in neutrophil CR3 function that occur during standard cell separation procedures. We have used it to investigate neutrophil functional abnormalities in B pseudomallei infection. The opportunity now exists to investigate the role of neutrophil CR3 function in other conditions.