Integrated catecholamine imaging in heart and lung across different cardiopulmonary disorders: A systems-based pilot analysis.

BACKGROUND: Autonomic nervous system deregulation is key in the progression of different cardiovascular diseases, and scintigraphic imaging with metaiodobenzilguanidine (MIBG) is the gold-standard its non-invasive evaluation. While heart catecholamine handling has been more extensively evaluated, fewer data are available on lung or combined cardiopulmonary MIBG uptake. The aim of this short communication is the simultaneous analysis of cardiopulmonary MIBG uptake to improve patients' characterization. METHODS: 126 subjects were retrospectively analyzed based on the underlying etiology (systolic heart failure -HF, n = 52; myocardial infarction - MI, n = 26; pulmonary arterial hypertension - PAH, n = 13; cardiac amyloidosis - CA, n = 14; candidates to transcatheter aortic valve replacement - pre-TAVI, n = 21). The cut-off values of 1.6 and 1.62 were chosen for cardiac and lung/mediastinum ratios, respectively. RESULTS: Combined alterations of MIBG uptake were found in 37% of patients. In HF and MI, simultaneous cardiopulmonary derangement was found in 40 and 46% of the patients, respectively, while in CA up to 65% of patients showed combined cardiopulmonary alterations. Conversely, patients with PAH mainly showed lung-only involvement (54%) and pre-TAVI patients cardiac-only alterations (24%). CONCLUSIONS: Simultaneous cardiopulmonary alterations of catecholamines handling are highly prevalent and may help to better characterize concurrent end-organ dysfunction in different diseases.

Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies.

Most patients survive acute myocardial infarction (MI). Yet this encouraging development has certain drawbacks: heart failure (HF) prevalence is increasing and patients affected tend to have more comorbidities worsening economic strain on healthcare systems and impeding effective medical management. The heart's pathological changes in structure and/or function, termed myocardial remodelling, significantly impact on patient outcomes. Risk factors like diabetes, chronic obstructive pulmonary disease, female sex, and others distinctly shape disease progression on the 'road to HF'. Despite the availability of HF drugs that interact with general pathways involved in myocardial remodelling, targeted drugs remain absent, and patient risk stratification is poor. Hence, in this review, we highlight the pathophysiological basis, current diagnostic methods and available treatments for cardiac remodelling following MI. We further aim to provide a roadmap for developing improved risk stratification and novel medical and interventional therapies.

Attenuation of epileptogenesis by 2-deoxy-d-glucose is accompanied by increased cerebral glucose supply, microglial activation and reduced astrocytosis.

RATIONALE: Neuronal excitability and brain energy homeostasis are strongly interconnected and evidence suggests that both become altered during epileptogenesis. Pharmacologic modulation of cerebral glucose metabolism might therefore exert anti-epileptogenic effects. Here we provide mechanistic insights into effects of the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) on experimental epileptogenesis by longitudinal 2-deoxy-2[18F]fluoro-d-glucose positron emission tomography ([18F]FDG PET) and histology. METHODS: To imitate epileptogenesis, 6 Hz-corneal kindling was performed in male NMRI mice by twice daily electrical stimulation for 21 days. Kindling groups were treated i.p. 1 min after each stimulation with either 250 mg/kg 2-DG (CoKi_2-DG) or saline (CoKi_vehicle). A separate group of unstimulated mice was treated with 2-DG (2-DG_only). Dynamic 60-min [18F]FDG PET/CT scans were acquired at baseline and interictally on days 10 and 17 of kindling. [18F]FDG uptake (%injected dose/cc) was quantified in predefined regions of interest (ROI) using a MRI-based brain atlas, and kinetic modelling was performed to evaluate glucose net influx rate Ki and glucose metabolic rate MRGlu. Furthermore, statistical parametric mapping (SPM) analysis was applied on kinetic brain maps. For histological evaluation, brain sections were stained for glucose transporter 1 (GLUT1), astrocytes, microglia, as well as dying neurons. RESULTS: Post-stimulation 2-DG treatment attenuated early kindling progression, indicated by a reduction of fully-kindled mice, and a lower overall percentage of type five seizures. While 2-DG treatment alone led to globally increased Ki and MRGlu values at day 17, kindling progression per se did not influence glucose turnover. Kindling accompanied by 2-DG treatment, however, resulted in regionally elevated [18F]FDG uptake as well as increased Ki at days 10 and 17 compared both to baseline and to the 2-DG_only group. In hippocampus and thalamus, higher MRGlu values were found in the CoKi_2-DG vs. the CoKi_vehicle group at day 17. t maps resulting from SPM analysis generally confirmed the results of the ROI analysis, and additionally revealed increased MRGlu restricted to the ventral hippocampus when comparing the CoKi_2-DG and the 2-DG_only group both at days 10 and, more distinct, day 17. Immunohistochemical staining showed an attenuated kindling-induced regional activation of astrocytes in the CoKi_2-DG group. Interestingly, 2-DG treatment alone (and also in combination with kindling, but not kindling alone) led to increased microglial activation scores, whereas neither staining of GLUT1 nor of dying neurons revealed any differences to untreated controls. CONCLUSIONS: Post-stimulation treatment with 2-DG exerts disease-modifying effects in the mouse 6 Hz corneal kindling model. The observed local increase in glucose supply and turnover, the alleviation of astroglial activation and the activation of microglia by 2-DG might contribute separately or in combination to its positive interference with epileptogenesis.

Expert System for Bone Scan Interpretation Improves Progression Assessment in Bone Metastatic Prostate Cancer.

INTRODUCTION: The bone scan index (BSI) was introduced as a quantitative tool for tumor involvement in bone of patients with metastatic prostate cancer (mPCa). The computer-aided diagnosis device for BSI analysis EXINIboneBSI seems to represent technical progress for the quantitative assessment of bone involvement. But it is not yet clear if the automated BSI (aBSI) could contribute to improved evaluation of progression in patients under antiandrogens or chemotherapy in contrast to the visual interpretation and/or conventional biomarkers such as the prostate-specific antigen (PSA). METHODS: In 49 mPCa patients, bone scans were performed initially and during different therapy courses. Scans were evaluated visually and by the artificial-neural-network-based expert system EXINIboneBSI. Progression of metastatic bone involvement was defined according to the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria in the visual interpretation. The computer-assisted interpretation was based on different cutoff values in relative changes of the aBSI. Additionally, assessments according to bone scanning were compared to changes in the PSA value as a potential surrogate for treatment response. RESULTS: Using a sensitive cutoff value (5% or 10%) for the relative aBSI increase led to significantly increased progression determination compared to the visual interpretation of bone scans (49% and 43% vs. 27%, p < 0.001). In 63% of the cases PSA and BSI changes matched, whereas in 18% progression was only indicated by the aBSI. A relative cutoff of 5% for the aBSI decrease could reclassify 47 serial scan pairs which were visually interpreted as stable into 22 progressive and 25 remissive scans. CONCLUSION: Distinct thresholds of the relative aBSI could help to better assess disease progression in mPCa patients. Manual corrections of the BSI values are not required in most cases. The aBSI could serve as a useful additional parameter for therapy monitoring in mPCa patients in the future.

The importance of a correct positioning of the heart using IQ-SPECT system with multifocal collimators in myocardial perfusion imaging: a phantom study.

BACKGROUND: We have recently validated a quarter-time protocol in Myocardial Perfusion Imaging named IQ-SPECT, whose basic principle is to implement a multifocal collimator; However, in clinical practice, it may sometimes be difficult to center the heart in the region of highest magnification of the multifocal collimators (the so-called sweet spot). We therefore aimed to evaluate whether a heart mispositioning may affect results in MPI. METHODS: We simulated a rest study with an anthropomorphic phantom with an in vivo distribution of 400 MBq [(99m)Tc]tetrofosmin, with and without a transmural defect (TD). For each set of images, we performed 5 acquisitions, one with a correct centering and with other 4 degrees of mispositioning. Raw data and reconstructed images were evaluated qualitatively and quantitatively, including no corrections, correction for attenuation, for scatter or for both. We assessed polar plot uniformity, LV wall thickness, and TD and cavity contrast. RESULTS: Images obtained either with a correct heart centering or with mild misposition showed no differences, both qualitatively and quantitatively. Those obtained with major mispositioning differed in uniformity and TD contrast depending on correction parameters. CONCLUSION: This is the first study investigating how a heart mispositioning can affect diagnostic accuracy with IQ-SPECT system. Mild-to-moderate mispositioning (≤2.5 cm) is unlikely to significantly affect results.