Regional cerebral hypometabolism on 18F-FDG PET/CT scan in delirium is independent of acute illness and dementia.

INTRODUCTION: Delirium is associated with new onset dementia and accelerated cognitive decline; however, its pathophysiology remains unknown. Cerebral glucose metabolism previously seen in delirium may have been attributable to acute illness and/or dementia. We aimed to statistically map cerebral glucose metabolism attributable to delirium. METHODS: We assessed cerebral glucose metabolism using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in sick, older patients with and without delirium, all without clinical dementia (N = 20). Strict exclusion criteria were adopted to minimize the effect of established confounders on FDG-PET. RESULTS: Patients with delirium demonstrated hypometabolism in the bilateral thalami and right superior frontal, right posterior cingulate, right infero-lateral anterior temporal, and left superior parietal cortices. Regional hypometabolism correlated with delirium severity and performance on neuropsychological testing. DISCUSSION: In patients with acute illness but without clinical dementia, delirium is accompanied by regional cerebral hypometabolism. While some hypometabolic regions may represent preclinical Alzheimer's disease (AD), thalamic hypometabolism is atypical of AD and consistent with the clinical features that are unique to delirium.

The heritability of amyloid burden in older adults: the Older Australian Twins Study.

OBJECTIVE: To determine the proportional genetic contribution to the variability of cerebral ß-amyloid load in older adults using the classic twin design. METHODS: Participants (n=206) comprising 61 monozygotic (MZ) twin pairs (68 (55.74%) females; mean age (SD): 71.98 (6.43) years), and 42 dizygotic (DZ) twin pairs (56 (66.67%) females; mean age: 71.14 (5.15) years) were drawn from the Older Australian Twins Study. Participants underwent detailed clinical and neuropsychological evaluations, as well as MRI, diffusion tensor imaging (DTI) and amyloid PET scans. Fifty-eight participants (17 MZ pairs, 12 DZ pairs) had PET scans with 11Carbon-Pittsburgh Compound B, and 148 participants (44 MZ pairs, 30 DZ pairs) with 18Fluorine-NAV4694. Cortical amyloid burden was quantified using the centiloid scale globally, as well as the standardised uptake value ratio (SUVR) globally and in specific brain regions. Small vessel disease (SVD) was quantified using total white matter hyperintensity volume on MRI, and peak width of skeletonised mean diffusivity on DTI. Heritability (h2) and genetic correlations were measured with structural equation modelling under the best fit model, controlling for age, sex, tracer and scanner. RESULTS: The heritability of global amyloid burden was moderate (0.41 using SUVR; 0.52 using the centiloid scale) and ranged from 0.20 to 0.54 across different brain regions. There were no significant genetic or environmental correlations between global amyloid burden and markers of SVD. CONCLUSION: Amyloid deposition, the hallmark early feature of Alzheimer's disease, is under moderate genetic influence, suggesting a major environmental contribution that may be amenable to intervention.

Alectinib is effective, safe and tolerable in an adolescent with stage IVB ALK-rearranged adenocarcinoma of the lung.

Anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been shown to have significant activity in ALK-rearranged non-small cell lung cancers (NSCLC). There are no data for alectinib's safety or efficacy in younger patients, though it is superior to crizotinib in adult trials. We present a 14-year old girl diagnosed with stage IV-B ALK-positive adenocarcinoma of the lung after presenting with cough and fever. She was commenced on alectinib at adult dose and has had sustained complete metabolic remission for 9 months. She is the youngest patient with lung adenocarcinoma to be treated with alectinib.

Nondiagnostic 99mTc-MAG3 Diuresis Renography Studies Caused by Propofol Sedation: A Case Series.

ABSTRACT: 99mTc-MAG3 diuresis renography is a noninvasive functional imaging technique used to assess clearance of radiotracer in a dilated urinary tract under high diuresis. It is commonly performed in patients to diagnose functionally significant urinary tract obstruction. In some pediatric patients, sedation is required to enable imaging. However, propofol, a commonly used IV sedative agent, is associated with altered renal hemodynamics. We report a case series of 3 pediatric patients at our institution who received propofol sedation to enable 99mTc-MAG3 diuresis renography using a F+0 protocol, outlining that some "abnormal" studies were in fact assessed to be nondiagnostic.

Efficacy of MEK inhibition in a recurrent malignant peripheral nerve sheath tumor.

The prognosis of recurrent malignant peripheral nerve sheath tumors (MPNST) is dismal, with surgical resection being the only definitive salvage therapy. Treatment with chemoradiation approaches has not significantly improved patient outcomes. Similarly, trials of therapies targeting MPNST genomic drivers have thus far been unsuccessful. Improved understanding of the molecular pathogenesis of MPNST indicates frequent activation of the mitogen-activated protein kinase (MAPK) cell signaling pathway. MEK inhibitors have shown activity in preclinical studies; however, their clinical efficacy has not been reported to date. We describe here a case of sustained complete response to MEK inhibition in an adolescent patient with a recurrent metastatic MPNST with multiple alterations in the MAPK pathway, guided by a precision oncology approach.

18F-Fluorodeoxyglucose PET/CT-Guided Palliative Radiotherapy Provides Durable Responses to Over a Dozen Sites of Disease in Relapsed Myeloid Sarcoma.

Myeloid sarcoma (MS) is a rare entity, and FDG PET/CT is a useful tool for staging at diagnosis and response assessment. We present a case of a 72-year-old woman diagnosed with multifocal extramedullary MS, using FDG PET/CT to guide palliative radiotherapy to 13 sites of disease over 2 separate relapses with complete and durable local responses and minimal toxicity. This case represents the largest reported burden of disease in MS successfully treated with FDG PET/CT-guided radiotherapy.

Impact of salvage treatment modalities in patients with positive FDG-PET/CT after R-CHOP chemotherapy for aggressive B-cell non-Hodgkin lymphoma.

INTRODUCTION: To compare outcomes of different salvage treatment modalities in patients with aggressive B-cell non-Hodgkin lymphoma (NHL) who remain FDG-PET positive after R-CHOP chemotherapy. Existing data on these patients with FDG-PET primary refractory disease are limited. METHODS: Patients with diffuse large B-cell lymphoma or grade 3 follicular lymphoma were retrospectively reviewed from the Prince of Wales Hospital databases. Eligibility criteria were: age≥18 years, treated with R-CHOP, with positive post-chemotherapy FDG-PET. Salvage treatment modalities were: radical radiotherapy (RT, dose≥30 Gy), high dose chemotherapy and autologous stem cell transplant (ASCT), or non-radical management. Survival was calculated from date of post-chemotherapy FDG-PET to last follow-up. RESULTS: Twenty-six patients from 2003-2015 met the inclusion criteria. Median age was 60 (range 19-84). Most had adverse baseline features: 21 (81%) stage III-IV, 24 (92%) bulky disease and nine (35%) skeletal involvement. Characteristics of PET-positivity post-chemotherapy were single site in 16 (62%), sites of prior bulk in 24 of 24, skeletal sites in five of nine, and able to be encompassed by RT in 21 (81%). Salvage treatment was: radical RT in 17 (65%), ASCT in four (15%) and non-radical in five (20%). Median follow-up of surviving patients was 31 months. Kaplan-Meier estimates of 3-year PFS and OS were 41% and 52%, respectively. By salvage modality, 3-year PFS was 51% for RT, 25% for ASCT and 20% for non-radical treatment, (P = 0.453); 3-year OS was respectively 65%, 25% and 40% (P = 0.173). CONCLUSION: Patients with FDG-PET positive disease after R-CHOP for aggressive B-cell NHL are salvageable with radiotherapy.

Deleterious effect of nitric oxide inhibition in chronic hepatopulmonary syndrome.

On the basis of limited experimental and clinical studies, increased activity of the vasodilatory nitric oxide-cyclic guanosine monophosphate pathway is considered to play a key role in the pathogenesis of hepatopulmonary syndrome. We report a 46-year-old woman with Child-Pugh class C cirrhosis and progressive dyspnoea for 12 months. Investigations revealed elevated circulating concentrations of nitric oxide metabolites and exhaled nitric oxide levels, an hyperdynamic circulation with low systemic vascular resistance and mean arterial pressure, a large right to left intrapulmonary shunt fraction on radiolabelled macroaggregated albumin perfusion scanning, positive contrast-enhanced echocardiography, reduced diffusion capacity of carbon monoxide, hypoxaemia and orthodeoxyia, all in keeping with severe hepatopulmonary syndrome. Sequential inhibition of the nitric oxide-cyclic guanosine monophosphate pathway using curcumin (diferuloylmethane), terlipressin and methylene blue was associated with substantial improvements in vascular tone and the hyperdynamic circulation. No improvement, however, in the intrapulmonary shunt was demonstrated. Both hypoxaemia and orthodeoxia were substantially, reproducibly and reversibly worsened with all three treatments. Our findings argue against the contention that intrapulmonary shunting and impairment in arterial oxygenation in hepatopulmonary syndrome are necessarily the consequence of on-going, nitric oxide-cyclic guanosine monophosphate-mediated vasodilatation, at least in the chronic stage, and, given the possibility of substantial worsening of pulmonary oxygen exchange, suggest that inhibition of the nitric oxide-cyclic guanosine monophosphate pathway should be avoided in this setting.

2-18F-fluoro-2-deoxyglucose positron emission tomography in delirium.

Delirium is a common, serious, yet poorly understood syndrome. Growing evidence suggests cerebral metabolism is fundamentally disturbed; however, it has not been investigated using 2-18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in delirium. This prospective study thus explored FDG PET patterns of cerebral glucose metabolism in older inpatients with delirium. A particular emphasis was on the posterior cingulate cortex (PCC), a key region for attention, which is a central feature of delirium. Delirium scans were compared with post-delirium scans using visual analysis and semi-quantitative analysis with NeuroQ; 13 participants (8 female, median 84 y) were scanned during delirium, and 6 scanned again after resolution. On visual analysis, cortical hypometabolism was evident in all participants during delirium (13/13), and improved with delirium resolution (6/6). Using NeuroQ, glucose metabolism was higher post-delirium in the whole brain and bilateral PCC compared to during delirium ( p < 0.05). Greater metabolism in both PCCs correlated with better performance on a neuropsychological test of attention, the WAIS-IV Digit Span Test forwards, and with shorter delirium duration. This research found widespread, reversible cortical hypometabolism during delirium and PCC hypometabolism was associated with inattention during delirium.

Pitfalls and artifacts in 18FDG PET and PET/CT oncologic imaging.

It is estimated that in excess of one million positron emission tomography (PET) scans are performed each year and PET can now truly be regarded as a routine imaging procedure in clinical management. Many potential pitfalls and artifacts have previously been described with (18)F-fluorodeoxyglucose PET imaging, but more continue to become apparent as worldwide experience increases. In addition, the advent of combined PET/CT scanners in clinical imaging practice has brought their own specific pitfalls and artifacts. It is essential that we learn these potential pitfalls so that patients can be optimally prepared for their scans and that accurate interpretation can be made.

2-deoxy-2-((18)F)fluoro-D-glucose positron emission tomography/computed tomography imaging in paediatric oncology.

Positron emission tomography (PET) is a minimally invasive technique which has been well validated for the diagnosis, staging, monitoring of response to therapy, and disease surveillance of adult oncology patients. Traditionally the value of PET and PET/computed tomography (CT) hybrid imaging has been less clearly defined for paediatric oncology. However recent evidence has emerged regarding the diagnostic utility of these modalities, and they are becoming increasingly important tools in the evaluation and monitoring of children with known or suspected malignant disease. Important indications for 2-deoxy-2-((18)F)fluoro-D-glucose (FDG) PET in paediatric oncology include lymphoma, brain tumours, sarcoma, neuroblastoma, Langerhans cell histiocytosis, urogenital tumours and neurofibromatosis type I. This article aims to review current evidence for the use of FDG PET and PET/CT in these indications. Attention will also be given to technical and logistical issues, the description of common imaging pitfalls, and dosimetric concerns as they relate to paediatric oncology.