Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype.

Several lines of study suggest that peripheral metabolism of amyloid beta (Aß) is associated with risk for Alzheimer disease (AD). In blood, greater than 90% of Aß is complexed as an apolipoprotein, raising the possibility of a lipoprotein-mediated axis for AD risk. In this study, we report that genetic modification of C57BL/6J mice engineered to synthesise human Aß only in liver (hepatocyte-specific human amyloid (HSHA) strain) has marked neurodegeneration concomitant with capillary dysfunction, parenchymal extravasation of lipoprotein-Aß, and neurovascular inflammation. Moreover, the HSHA mice showed impaired performance in the passive avoidance test, suggesting impairment in hippocampal-dependent learning. Transmission electron microscopy shows marked neurovascular disruption in HSHA mice. This study provides causal evidence of a lipoprotein-Aß /capillary axis for onset and progression of a neurodegenerative process.

Association between ageing, brain chemistry and white matter volume revealed with complementary MRI and FTIR brain imaging.

Magnetic resonance imaging (MRI) is the gold standard method to study brain anatomy in vivo. Using MRI, subtle alterations to white matter structures in the brain are observed prior to cognitive decline associated with the ageing process, and neurodegenerative diseases such as Alzheimer's disease. Detection of such alterations provides hope for early clinical diagnosis. While MRI is essential to detect subtle alterations to brain structure in vivo, the technique is less suited to study and image the distribution of biochemical markers within specific brain structures. Consequently, the chemical changes that drive, or are associated with MRI-detectable alterations to white matter are not well understood. Herein, we describe (to the best of our knowledge) the first application of a complementary imaging approach that incorporates in vivo MRI with ex vivo Fourier transform infrared (FTIR) spectroscopic imaging on the same brain tissue. The combined workflow is used to detect and associate markers of altered biochemistry (FTIR) with anatomical changes to brain white matter (MRI). We have applied this combination of techniques to the senescence accelerated murine prone strain 8 (SAMP8) mouse model (n = 6 animals in each group, analysed across two ageing time points, 6 and 12 months). The results have demonstrated alterations to lipid composition and markers of disturbed metabolism during ageing are associated with loss of white matter volume.

Correlation between circulating tumour DNA and metabolic tumour burden in metastatic melanoma patients.

BACKGROUND: Circulating tumour DNA (ctDNA) may serve as a measure of tumour burden and a useful tool for non-invasive monitoring of cancer. However, ctDNA is not always detectable in patients at time of diagnosis of metastatic disease. Therefore, there is a need to understand the correlation between ctDNA levels and the patients' overall metabolic tumour burden (MTB). METHODS: Thirty-two treatment naïve metastatic melanoma patients were included in the study. MTB and metabolic tumour volume (MTV) was measured by 18F-fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT). Plasma ctDNA was quantified using droplet digital PCR (ddPCR). RESULTS: CtDNA was detected in 23 of 32 patients. Overall, a significant correlation was observed between ctDNA levels and MTB (p < 0.001). CtDNA was not detectable in patients with an MTB of ≤10, defining this value as the lower limit of tumour burden that can be detected through ctDNA analysis by ddPCR. CONCLUSIONS: We showed that ctDNA levels measured by ddPCR correlate with MTB in treatment naïve metastatic melanoma patients and observed a limit in tumour size for which ctDNA cannot be detected in blood. Nevertheless, our findings support the use of ctDNA as a non-invasive complementary modality to functional imaging for monitoring tumour burden.

Voltage-gated potassium channel antibody limbic encephalitis: a case illustrating the neuropsychiatric and PET/CT features with clinical and imaging follow-up.

OBJECTIVE: To illustrate the neuropsychiatric and imaging findings in a confirmed case of voltage-gated potassium channel antibody limbic encephalitis. METHOD: Case report and review of the literature. RESULTS: A 64-year-old man presented with several months' history of obsessive thoughts and compulsions associated with faciobrachial dystonic seizures. He had no significant past medical and psychiatric history. Physical examinations revealed only mildly increased tone in the left upper limb. Bedside cognitive testing was normal. Positron-emission tomography showed intense symmetrical uptake in the corpus striatum. No underlying malignancy was identified on whole body imaging. Magnetic resonance imaging, lumbar puncture and electroencephalogram were normal. Serum voltage-gated potassium channel antibodies were strongly positive. The patient had a favourable response to antiepileptic drugs, oral steroids and immunotherapy. CONCLUSIONS: Voltage-gated potassium channel limbic encephalitis characteristically presents with neuropsychiatric symptoms and temporal lobe seizures. Positron-emission tomography-computed tomography can be a useful adjunct to the clinical and biochemical work-up.

68Ga DOTATATE PET/CT of Non-FDG-Avid Pulmonary Metastatic Hemangiopericytoma.

We present the FDG and Ga DOTATATE PET/CT findings of a 68-year-old woman with pulmonary metastases 28 years after her initial diagnosis of central nervous system hemangiopericytoma. The largest of the pulmonary lesions showed prominent Ga DOTATATE uptake with comparatively minimal FDG avidity. Hemangiopericytoma is a rare mesenchymal tumor that arises from malignant pericytes, cells that form the walls of capillaries and postcapillary venules. This case demonstrates the potential of radiolabeled somatostatin analogs as a therapeutic option in the setting of widespread metastatic disease.

Alternative sites of injection for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Sentinel node biopsy is rapidly gaining popularity as a less invasive approach to nodal staging in breast cancer. The optimal route of injection of radiocolloids and dye is controversial. The purpose of the present paper was to review and assess the literature. METHODS: A MEDLINE search for reports of studies involving different injection sites of colloid and/or dye was performed. RESULTS: Although controversial, current evidence suggests that subareolar (SA) or intradermal/subdermal (ID/SD) injection will map the same axillary sentinel nodes (SN) as peritumoral (PT) injection in the vast majority of cases, is at least as successful, and is better logistically. Peritumoral, but not alternative routes, identify extra-axillary sentinel nodes, which are important in a minority of patients. CONCLUSIONS: It is recommended that at least some of the radiocolloid be injected peritumorally to avoid missing those SN not located in the ipsilateral axilla. Injection of the dye and a portion of radiocolloid in an ID/SA location is reasonable to take advantage of the general ease and accuracy of ID/SA injections in identifying axillary SN.