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Objective: Neuroinflammation is considered a key driver for neurodegeneration in several neurological diseases, including amyotrophic lateral sclerosis (ALS). SOD1 mutations cause about 20% of familial ALS, and related pathology might generate microglial activation triggering neurodegeneration. 11C-PK11195 is the prototypical and most validated PET radiotracer, targeting the 18-kDa translocator protein which is overexpressed in activated microglia. In this study, we investigated microglia activation in asymptomatic (ASYM) and symptomatic (SYM) SOD1 mutated carriers, by using 11C-PK11195 and PET imaging. Methods: We included 20 subjects: 4 ASYM-carriers, neurologically normal, 6 SYM-carriers with probable ALS, and 10 healthy controls. A receptor parametric mapping procedure estimated 11C-PK11195 binding potentials and voxel-wise statistical comparisons were performed at group and single-subject levels. Results: Both the SYM- and ASYM-carriers showed significant microglia activation in cortical and subcortical structures, with variable patterns at individual level. Clusters of activation were present in occipital and temporal regions, cerebellum, thalamus, and medulla oblongata. Notably, SYM-carriers showed microglia activation also in supplementary and primary motor cortices and in the somatosensory regions. Interpretation: In vivo neuroinflammation occurred in all SOD1 mutated cases since the presymptomatic stages, as shown by a significant cortical and subcortical microglia activation. The involvement of sensorimotor cortex became evident at the symptomatic disease stage. Although our data indicate the role of in vivo PET imaging for assessing resident microglia in the investigation of SOD1-ALS pathophysiology, further studies are needed to clarify the temporal and spatial dynamics of microglia activation and its relationship with neurodegeneration.

Quantification of amyloid PET studies is most accurate if regions of interest (ROIs) are not affected by the presence of cerebrospinal fluid. Patients with high amyloid load often have great atrophy, therefore, the use of atlas-based ROIs, instead of patient specific anatomy, can underestimate amyloid load, leading to a bias. Traditionally, this can be overcome only using MR anatomical sequences, which are burdensome and might not be ideal to be performed for each patient in the clinical routine. In this work, we propose to overcome this issue by using a method based on deep learning. As CT scans provide anatomical information, even at the very low doses used for PET attenuation correction, we propose the use of such a scan, together with the PET one, for a U-NET based segmentation. The approach achieves a median DICE score of 77% on a validation cohort of N=20 patients, even when using only N=14 patients in the training dataset. A dedicated data augmentation strategy is used, and the individual contribution of each modality is analyzed. We find that the joint effect of PET and CT is beneficial (median DICE: PET only 73.0%, CT only 74%). A near perfect correlation with MR-based quantification was also found.

We studied the relationships between coronary anatomy, perfusion and metabolism in myocardial segments exhibiting transient and persistent perfusion defects on stress/rest 99Tcm-MIBI single photon emission tomography in 35 patients (31 males, 4 females, mean age 56 ± 7 years) with a previous myocardial infarction. Quantitative coronary angiography and assessment of myocardial perfusion reserve and glucose metabolism were performed within 1 week of one another. Perfusion was assessed by SPET after the intravenous injection of 740 MBq of 99Tcm-MIBI at rest and after exercise. Regional myocardial glucose metabolism was assessed by position emission tomography at rest (200 MBq of 18F-2-deoxyglucose, FDG) after an overnight fast with no glucose loading. All 35 patients exhibited persistent perfusion defects consistent with the clinically identified infarct site, and 27 (77%) also showed various degrees of within-infarct FDG uptake; 11 patients developed exercise-induced transient perfusion defects within, or in the vicinity of, 15 infarct segments and resting FDG uptake was present in 10 of these segments (67%). Five patients also showed exercise-induced transient perfusion defects in nine segments remote from the site of infarct: resting FDG uptake was present in six of these regions (67%). Finally, nine patients had increased glucose uptake in non-infarcted regions not showing transient perfusion defects upon exercise—testing and perfused by coronary arteries with only minor irregularities. Our results confirm the presence-of viable tissue in a large proportion of infarct sites. Moreover, FDG uptake can be seen in regions perfused by coronary arteries showing minor irregularities, not necessarily resulting in detectable transient perfusion defects on a MIBI stress scan. Since the clinical significance of such findings is not clear, further studies should be conducted to assess the long-term evolution of perfusion, function and metabolism in non-revascularized patients

The distinction between fibrotic and viable myocardium is a key issue in patients with coronary artery disease and left ventricular dysfunction. Metabolic imaging with positron emission tomography (PET) and labeled tracers, along with the study of myocardial perfusion, is now available to identify hibernating myocardium. However, PET imaging of myocardial metabolism is a high-cost and time-consuming technique, and requires an on-site cyclotron. The aim of this study is to test the reliability of dobutamine echocardiography (DE) compared with PET imaging, for the identification of hibernating myocardium. In 16 patients, scheduled for myocardial revascularization, left ventricular shapes were divided in eight segments both for echocardiographic and nuclear study evaluation. All patients underwent a technetium 99m MIBI single-photon emission tomography stress-rest study of perfusion, a fluorine-18-labeled deoxyglucose (FDG(/PET study of metabolism, and a DE test (baseline, at a 5 micrograms/kg/min infusion of dobutamine for 8 minutes and at a 10 micrograms/kg/min dose for additional 8 minutes). Neither myocardial ischemia nor arrhythmia occurred during the DE test. Baseline echocardiograms showed 90 segments with wall motion abnormalities: wall motion impairment was decreased or reversed in 33 of 90 segments; it remained unchanged in 57 of 90 segments. In 32 of 33 segments considered viable on the basis of DE and in 21 of 57 segments with unchanged kinesis, some degree of FDG was detected. Thus, sensitivity and specificity of DE compared with nuclear studies was 60% and 97% respectively. Moreover, a good correlation and agreement (kappa = 0.51) between DE and the presence of FDG were found. We conclude that DE is a safe and reliable test for the screening of hibernating myocardium in patients with chronic coronary artery disease and left ventricular dysfunction.

The relationships between rest conditions of myocardial asynergy, response to dobutamine administration, perfusion and glucose metabolism were examined in 12 patients with chronic coronary artery disease and left ventricular dysfunction. We evaluated (1) rest and stress myocardial perfusion by 99Tcm-methoxyisobutylisonitrile (MIBI) and single photon emission tomography (SPET), (2) rest myocardial segmental wall motion by trans-thoracic echocardiography and low-dose dobutamine, and (3) myocardial metabolism by [18F]-2-fluoro-2-deoxy-D-glucose (18-FDG) and positron emission tomography (PET), in the fasting state. The analysis was carried out on 16 left ventricular myocardial segments. The SPET studies were analysed semi-quantitatively by normalization to the peak activity. Wall motion was assessed by a visual score. An 18FDG index was determined as the tissue/blood pool radioactivity ratio in each segment. The results showed: (1) remarkably good agreement between the number of dobutamine responsive segments and 18FDG positive segments among those that were only moderately hypoperfused and hypokinetic; (2) a smaller number of dobutamine responsive segments than 18FDG positive segments among those that were hypoperfused and akinetic; and (3) the presence of 18FDG in 50% of the segments that were severely hypoperfused and akinetic or dyskinetic and without improvement with dobutamine. These results indicate that in severely hypoperfused and akinetic or dyskinetic segments, trans-thoracic echocardiography under inotropic stimulation provides little additional information compared with that obtained with rest echocardiography and perfusion studies; the assessment of 18FDG uptake provides information that is complementary to that obtained by perfusion assessment, rest and dobutamine trans-thoracic echocardiography.

Technetium(III)-99m-Q12, trans-(1,2-bis(dihydro-2,2,5,5-tetramethyl- 3(2H)furanone-4-methyleneimino)ethane)bis(tris(3-methoxy-1-propyl)- phosphine)technetium(III)-99m, is a nonreducible complex of Tc(III) which is herein evaluated as a myocardial perfusion imaging agent. Methods: The biodistribution and dosimetry of 99mTc-Q12 were assessed in 10 normal volunteers, while its potential clinical use was evaluated in 70 patients. Results: Safety parameters measured up to 24 hr postinjection demonstrate no clinically significant drug-related adverse reactions. Technetium(III)-99m- Q12 exhibits good heart uptake (2.2% injected dose at 1 hr postinjection under resting conditions) and no detectable myocardial washout or redistribution up to 5 hr postinjection. The biodistribution is characterized by very rapid hepatobiliary clearance which allows effective myocardial imaging at times as short as 15 min postinjection. Blood and plasma clearances and myocardial uptake are rapid, while lung uptake is minimal. The heart-to-lung and heart-to-liver ratios are higher at stress than at rest, independent of the time elapsed between injection and image acquisition, and independent of whether the patient is fasted or fed after tracer administration. A preliminary correlation shows that 46/47 patients with angiographically demonstrated CAD also have perfusion defects demonstrated by 99mTc-Q12. Conclusions: On the basis of the studies reported herein, 99mTc-Q12 appears to be a promising myocardial perfusion imaging agent

We examined 17 angina-free patients with left ventricular dysfunction, referred for surgical decision-making, who presented with no or few signs and symptoms of myocardial ischemia according to treadmill stress test. On cardiac catheterization they were affected by severe multi-vessel coronary artery disease; the mean left end-diastolic pressure of this population was 26.3 +/- 5.5 mm Hg (mean +/- SD) and their mean ejection fraction was 27.6 +/- 4.9% (mean +/- SD). They all were investigated for the presence of viable myocardium by the combined assessment of cardiac perfusion and metabolism using single photon emission tomography with [99mTc] labelled hexakis-2-methoxy-isobutyl-isonitrile [99mTc]MIBI/SPET) and positron emission tomography with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG/PET), respectively. Patients were considered for coronary surgery when [18F]FDG was detectable in at least two cardiac segments with wall motion abnormalities and perfusion defects. Nine patients were operated on, six were medically treated and two were scheduled for heart transplantation. We recorded no in-hospital mortality. At a mean follow-up of 28.4 +/- 9.8 (mean +/- SD) months all surgical patients were alive and their NYHA functional classes have improved, except in one case. Among the patients refused for bypass surgery, three are in stable conditions, three have worsened clinical statuses and two died while waiting for heart transplantation. In conclusion, for patients with bypassable coronaries, left ventricular dysfunction and lack of angina, successful coronary revascularization may be predicted by the presence of viable myocardium demonstrated with positron emission tomography.

We tested the possibility of identifying areas of hibernating myocardium by the combined assessment of perfusion and metabolism using single photon emission tomography (SPET) with technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) and positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG). Segmental wall motion, perfusion and 18F-FDG uptake were scored in 5 segments in 14 patients with coronary artery disease (CAD), for a total number of 70 segments. Each subject underwent the following studies prior to and following coronary artery bypass grafting (CABG): first-pass radionuclide angiography, electrocardiography gated planar perfusion scintigraphy and SPET perfusion scintigraphy with 99mTc-MIBI and, after 16 h fasting, 18F-FDG/PET metabolic scintigraphy. Wall motion impairment was either decreased or completely reversed by CABG in 95% of the asynergic segments which exhibited 18F-FDG uptake, whereas it was unmodified in 80% of the asynergic segments with no 18F-FDG uptake. A stepwise multiple logistic analysis was carried out on the asynergic segments to estimate the postoperative probability of wall motion improvement on the basis of the preoperative regional perfusion and metabolic scores. The segments with the highest probability (96%) of functional recovery from preoperative asynergy after revascularization were those with a marked 18F-FDG uptake prior to CABG. High probabilities of functional recovery were also estimated for the segments presenting with moderate and low 18F-FDG uptake (92% and 79%, respectively). A low probability of functional recovery (13%) was estimated in the segments with no 18F-FDG uptake.