The Role of Scintigraphy with Bone Radiotracers in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is caused by the myocardial deposition of misfolded proteins, either amyloid transthyretin (ATTR) or immunoglobulin light chains (AL). The paradigm of this condition has transformed, since CA is increasingly recognized as a relatively prevalent cause of heart failure. Cardiac scintigraphy with bone tracers is the unique noninvasive technique able to confirm CA without performing tissue biopsy or advanced imaging tests. A moderate-to-intense myocardial uptake (Perugini grade ≥2) associated with the absence of a monoclonal component is greater than 99% specific for ATTR-CA, while AL-CA confirmation requires tissue biopsy.

An Explainable Convolutional Neural Network for the Early Diagnosis of Alzheimer's Disease from 18F-FDG PET.

Convolutional Neural Networks (CNN) which support the diagnosis of Alzheimer's Disease using 18F-FDG PET images are obtaining promising results; however, one of the main challenges in this domain is the fact that these models work as black-box systems. We developed a CNN that performs a multiclass classification task of volumetric 18F-FDG PET images, and we experimented two different post hoc explanation techniques developed in the field of Explainable Artificial Intelligence: Saliency Map (SM) and Layerwise Relevance Propagation (LRP). Finally, we quantitatively analyze the explanations returned and inspect their relationship with the PET signal. We collected 2552 scans from the Alzheimer's Disease Neuroimaging Initiative labeled as Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and Alzheimer's Disease (AD) and we developed and tested a 3D CNN that classifies the 3D PET scans into its final clinical diagnosis. The model developed achieves, to the best of our knowledge, performances comparable with the relevant literature on the test set, with an average Area Under the Curve (AUC) for prediction of CN, MCI, and AD 0.81, 0.63, and 0.77 respectively. We registered the heatmaps with the Talairach Atlas to perform a regional quantitative analysis of the relationship between heatmaps and PET signals. With the quantitative analysis of the post hoc explanation techniques, we observed that LRP maps were more effective in mapping the importance metrics in the anatomic atlas. No clear relationship was found between the heatmap and the PET signal.

Bayesian Convolutional Neural Networks in Medical Imaging Classification: A Promising Solution for Deep Learning Limits in Data Scarcity Scenarios.

Deep neural networks (DNNs) have already impacted the field of medicine in data analysis, classification, and image processing. Unfortunately, their performance is drastically reduced when datasets are scarce in nature (e.g., rare diseases or early-research data). In such scenarios, DNNs display poor capacity for generalization and often lead to highly biased estimates and silent failures. Moreover, deterministic systems cannot provide epistemic uncertainty, a key component to asserting the model's reliability. In this work, we developed a probabilistic system for classification as a framework for addressing the aforementioned criticalities. Specifically, we implemented a Bayesian convolutional neural network (BCNN) for the classification of cardiac amyloidosis (CA) subtypes. We prepared four different CNNs: base-deterministic, dropout-deterministic, dropout-Bayesian, and Bayesian. We then trained them on a dataset of 1107 PET images from 47 CA and control patients (data scarcity scenario). The Bayesian model achieved performances (78.28 (1.99) % test accuracy) comparable to the base-deterministic, dropout-deterministic, and dropout-Bayesian ones, while showing strongly increased "Out of Distribution" input detection (validation-test accuracy mismatch reduction). Additionally, both the dropout-Bayesian and the Bayesian models enriched the classification through confidence estimates, while reducing the criticalities of the dropout-deterministic and base-deterministic approaches. This in turn increased the model's reliability, also providing much needed insights into the network's estimates. The obtained results suggest that a Bayesian CNN can be a promising solution for addressing the challenges posed by data scarcity in medical imaging classification tasks.

18-FDG PET for large vessel vasculitis diagnosis and follow-up.

OBJECTIVES: Large vessel vasculitis (LVV) are chronic inflammatory diseases that affect arteries. While a mere clinical-serological approach does not seem sensitive either in the initial evaluation nor in long-term monitoring, 18-FDG positron emission tomography (18-FDG PET) is currently considered a useful assessment tool in LVV. We aimed at exploring the utility of 18-FDG, compared with traditional assessments, in the short- and long-term follow-up of patients with LVV. In addition, we compared patterns of vascular involvement in patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA). METHODS: We retrospectively analysed 47 patients affected by LVV, evaluating clinics, blood chemistry and 18-FDG PET results, at two time points, short-term (average 8 months after diagnosis) and long-term (average 29 months). RESULTS: 18-FDG PET uptake, expressed as mean value of SUV max, decreased significantly during follow-up in all the patients. A low concordance between 18-FDG PET and acute phase reactants levels was observed, but also a good sensitivity in detecting the response to treatment. CONCLUSIONS: The results confirm the role of 18-FDG PET as a powerful tool in the evaluation of LVV, both at the time of diagnosis and during monitoring. Furthermore, the data confirm that GCA and TAK are part of the same disease spectrum.

Accuracy of 99mTc-Hydroxymethylene diphosphonate scintigraphy for diagnosis of transthyretin cardiac amyloidosis.

BACKGROUND AND AIM: Either 99mTechnetium diphosphonate (Tc-DPD) or pyrophosphate (Tc-PYP) scintigraphy plays a relevant role in diagnosing transthyretin cardiac amyloidosis (CA), and labeled radiotracers have been extensively studied in diagnosing CA. Few studies have analyzed and validated 99mTc-Hydroxymethylene diphosphonate (Tc-HMDP). Our aim was to validate the diagnostic accuracy of Tc-HMDP total-body scintigraphy in a cohort of patients with biopsy-proven transthyretin CA. METHODS AND RESULTS: We retrospectively evaluated all patients undergoing 99mTc-HMDP total-body scintigraphy, in adjunct to a comprehensive diagnostic work-up for suspected CA. Sixty-five patients were finally diagnosed with CA, while it was excluded in 20 subjects with left ventricular hypertrophy of various etiologies. Twenty-six patients had AL-CA, 39 had TTR CA (16 TTRm, 23 TTRwt). At Tc-HMDP scintigraphy, 2 AL patients showed a Perugini score grade 1 heart uptake, while 24 showed no uptake. All TTR patients showed Tc-HMDP uptake, with three patients showing a Perugini score grade 1, 16 grade 2, and 20 grade 3, respectively. No uptake was observed in patients with left ventricular hypertrophy. A positive Tc-HMDP scintigraphy showed a 100% sensitivity and a 96% specificity for TTR CA identification. CONCLUSIONS: Tc-HMDP scintigraphy is as accurate as Tc-DPD or Tc-PYP, and may therefore de facto be considered a valuable tool for the diagnosis of TTR CA.

Effect of prolonged fasting and low molecular weight heparin or warfarin therapies on 2-deoxy-2-[18F]-fluoro-D-glucose PET cardiac uptake.

BACKGROUND: Whether anticoagulants other than unfractionated heparin are able to suppress cardiac PET uptake of 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) is unknown. METHODS: One-hundred-seventy-four patients without history and clinical evidence of cardiac dysfunction and/or coronary heart disease underwent a 18F-FDG PET/CT study. All patients were studied with a >12-hours fasting and divided into 2 groups: group-1 without anticoagulant therapy (n:75); group-2 patients on low molecular weight heparin (n:60) or warfarin therapy (n:39). Cardiac 18F-FDG uptake was estimated qualitatively using a 4-point scale and semiquantitatively as total LV glycolysis (LVG) and metabolic volume (MV), drawing isocontour volume of interest (VOI) including the whole LV. RESULTS: Qualitatively, LV 18-FDG uptake was scored 0 or 1, indicating a good suppression, in 10/75 (13%) patients of group-1 and 77/99 (78%) of group-2 (p < .001). Semiquantitatively, patients of group-1 showed higher values of 18-FDG uptake than patients of group-2, assessed as LVG (802,649 ± 468,442 vs 198,989 ± 261,439, p < .0001) or MV (219 ± 77 vs 57 ± 48 cm3, p < .0001). Subanalysis for anticoagulant drugs showed similar results. CONCLUSIONS: Prolonged fasting combined to anticoagulants other than unfractionated heparin is able to minimize glucose cardiac metabolism. Our data confirm previous observation on the possibility to influence the metabolic pattern of the heart before the PET scan and broadens the spectrum of pharmacological options.

PET-CT evaluation of amyloid systemic involvement with [18F]-florbetaben in patient with proved cardiac amyloidosis: a case report.

BACKGROUND: One of the most frequent disorders which lead to cardiac amyloidosis is transthyretin-related amyloidosis (ATTR). Some PET radio-pharmaceuticals for the detection of beta-amyloid deposits within the brain have shown to be able to detect also cardiac amyloid deposits. We present a case of a man with ATTR studied with [18F]-florbetaben PET-CT. RESULTS: Total-body scan showed a moderate uptake in the bone marrow, especially in correspondence of the vertebral column, while no significant myocardial uptake was present. Cardiac-focused scans showed low mean cardiac SUV values confirming the absence of significant myocardial uptake. Brain scan showed a significant cortical brain uptake of the radio-pharmaceutical more evident in correspondence of frontal and temporal lobes. CONCLUSIONS: Distinct subtypes of amyloidosis show different uptake of the radiotracer. Brain amyloid deposition in the presence of a systemic disease could not be caused by the same amyloid precursor.

Association between left ventricular regional sympathetic denervation and mechanical dyssynchrony in phase analysis: a cardiac CZT study.

PURPOSE: To evaluate the relationships among myocardial sympathetic innervation, perfusion and mechanical synchronicity assessed with cardiac cadmium-zinc-telluride (CZT) scintigraphy. METHODS: A group of 29 patients underwent an evaluation of myocardial perfusion with (99m)Tc-tetrofosmin CZT scintigraphy and adrenergic innervation with (123)I-metaiodobenzylguanidine (MIBG) CZT scintigraphy. The summed rest score (SRS), motion score (SMS) and thickening score (STS), as well as the summed (123)I-MIBG defect score (SS-MIBG), were determined. Regional tracer uptake for both (99m)Tc-tetrofosmin and (123)I-MIBG was also calculated. Finally, the presence of significant myocardial mechanical dyssynchrony was evaluated in phase analysis on gated CZT images and the region of latest mechanical activation identified. RESULTS: Significant mechanical dyssynchrony was present in 17 patients (59 %) and associated with higher SRS (P = 0.030), SMS (P < 0.001), STS (P = 0.003) and early SS-MIBG (P = 0.037) as well as greater impairments in left ventricular ejection fraction (P < 0.001) and end-diastolic volume (P < 0.001). In multivariate analysis a higher end-diastolic volume remained the only predictor of mechanical dyssynchrony (P = 0.047). Interestingly, while in the whole population regional myocardial perfusion and adrenergic activity were strongly correlated (R = 0.68), in patients with mechanical dyssynchrony the region of latest mechanical activation was predicted only by greater impairment in regional (123)I-MIBG uptake (P = 0.012) that overwhelmed the effect of depressed regional perfusion. CONCLUSION: Left ventricular mechanical dyssynchrony is associated with greater depression in contractile function and greater impairments in regional myocardial perfusion and sympathetic activity. In patients with dyssynchrony, the region of latest mechanical activation is characterized by a significantly altered adrenergic tone.

Wild-Type Transthyretin Cardiac Amyloidosis is Not Rare in Elderly Subjects: the CATCH Screening Study.

BACKGROUND: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) affects older adults and is currently considered as a rare disorder. OBJECTIVE: We investigated for the first time the prevalence of ATTRwt-CA in elderly individuals from the general population. METHODS: General practitioners from Pisa, Italy, proposed a screening for ATTRwt-CA to all their patients aged 65-90 years, until 1,000 accepted. The following red flags were searched: interventricular septal thickness ≥12 mm, any echocardiographic, ECG or clinical hallmark of CA, or high sensitivity-troponin T ≥14 ng/L. Individuals with at least one red flag (n=346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted. RESULTS: Four patients received a non-invasive diagnosis of ATTRwt-CA. All complained of dyspnea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (grade 3), left ventricular (LV) wall thickening, grade 2 to 3 diastolic dysfunction, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >1,000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT-proBNP <300 ng/L. The prevalence of ATTR-CA in subjects ≥65 years was calculated as 0.46% (i.e., 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2). CONCLUSIONS: ATTRwt-CA is uncommon in elderly subjects from the general population, but more frequent than expected for a rare disease.

Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is a heart condition mostly found in older adults. ATTRwt-CA is considered a rare disease, although no systematic screening have been performed yet. The study aimed to understand how common this disease is among the general population aged 65 to 90 years in Pisa, Italy. To do this, general practitioners offered screening for ATTRwt-CA to their patients within this age group. The initial step of the screening involved checking for certain warning signs (red flags), like abnormal thickness in a part of the heart called the interventricular septum, unusual heart function observed through various tests, or elevated levels of a specific heart protein. Out of 1,000 individuals who began the screening process, 346 showed at least one of these red flags and were further examined using bone scintigraphy (a type of imaging test) and tests for a specific protein related to this condition. Of these, 216 agreed to proceed with these additional tests. The results showed that four of these patients actually had ATTRwt-CA. Their conditions varied in severity, with some showing more intense signs of the disease on the heart scans, thicker heart walls, and higher levels of heart stress proteins. All four patients experienced mild difficulty in breathing during physical activity. Based on these findings, the study concluded that about 0.46% of elderly individuals in the general population might have ATTRwt-CA, indicating that the disease is somewhat more common in this age group than previously thought.

Gender differences in the evaluation of coronary artery disease with a cadmium-zinc telluride camera.

PURPOSE: Coronary artery disease remains one of the most significant causes of morbidity and mortality among women. The published literature shows the importance of standard single photon emission computed tomography in the evaluation of women with known or suspected ischaemic heart disease, in terms of target intervention and clinical treatment. The purpose of the present study was to ascertain the diagnostic accuracy of cadmium-zinc-telluride (CZT) myocardial perfusion imaging according to gender, within a prospective database of patients with known or suspected coronary artery disease, using coronary angiography as the reference standard. METHODS: Included in the study were 309 consecutive patients, of whom 248 were men (80 %), with known or suspected coronary artery disease and who had been referred to our laboratory for stress-rest myocardial perfusion imaging. All patients underwent coronary angiography within 30 days. All patients underwent a single-day stress-rest low-dose ultrafast protocol. Fifteen minutes after the end of the stress (dose range 185 to 222 MBq of (99m)Tc-tetrofosmin), all patients underwent the first scan with an acquisition time of 7 min. The rest scan (dose range 370 to 444 MBq of (99m)Tc-tetrofosmin) was acquired from 30 min to 45 min after injection, with an acquisition time of 6 min. Images were visually inspected, and summed stress scores (SSS) and summed rest scores (SRS) were obtained. RESULTS: Image quality was graded "good" or better in more than 90 % of patients. On coronary angiography, left main trunk stenosis, left anterior descending artery stenosis, left circumflex artery stenosis and right coronary artery stenosis were seen in 3, 155 , 142 and 131 patients, respectively. In women, the mean SSS and SRS were 8 ± 5 and 3 ± 1, respectively. Semiquantitative regional and global SSS were good discriminants of coronary artery disease, and the overall area under the receiver operator characteristic (ROC) curve was 0.822 (95 % CI 0.685 - 0.959). The value was comparable to that obtained in men (overall ROC area 0.884, 95 % CI 0.836 - 0.933). CONCLUSION: A low-dose protocol with a CZT camera can be routinely used in women with known or suspected coronary artery disease without loss of accuracy and with lower radiation exposure of the patients.

Gated SPECT evaluation of left ventricular function using a CZT camera and a fast low-dose clinical protocol: comparison to cardiac magnetic resonance imaging.

PURPOSE: CZT technology allows ultrafast low-dose myocardial scintigraphy but its accuracy in assessing left ventricular function is still to be defined. METHODS: The study group comprised 55 patients (23 women, mean age 63 ± 9 years) referred for myocardial perfusion scintigraphy. The patients were studied at rest using a CZT camera (Discovery NM530c; GE Healthcare) and a low-dose (99m)Tc-tetrofosmin clinical protocol (mean dose 264 ± 38 MBq). Gated SPECT imaging was performed as a 6-min list-mode acquisition, 15 min after radiotracer injection. Images were reformatted (8-frame to 16-frame) using Lister software on a Xeleris workstation (GE Healthcare) and then reconstructed with a dedicated iterative algorithm. Analysis was performed using Quantitative Gated SPECT (QGS) software. Within 2 weeks patients underwent cardiac magnetic resonance imaging (cMRI, 1.5-T unit CVi; GE Healthcare) using a 30-frame acquisition protocol and dedicated software for analysis (MASS 6.1; Medis). RESULTS: The ventricular volumes obtained with 8-frame QGS showed excellent correlations with the cMRI volumes (end-diastolic volume (EDV), r = 0.90; end-systolic volume (ESV), r = 0.94; p < 0.001). However, QGS significantly underestimated the ventricular volumes (mean differences: EDV, -39.5 ± 29 mL; ESV, -15.4 ± 22 mL; p < 0.001). Similarly, the ventricular volumes obtained with 16-frame QGS showed an excellent correlations with the cMRI volumes (EDV, r = 0.92; ESV, r = 0.95; p < 0.001) but with significant underestimations (mean differences: EDV, -33.2 ± 26 mL; ESV, -17.9 ± 20 mL; p < 0.001). Despite significantly lower values (47.9 ± 16 % vs. 51.2 ± 15 %, p < 0.008), 8-frame QGS mean ejection fraction (EF) was closely correlated with the cMRI values (r = 0.84, p < 0.001). The mean EF with 16-frame QGS showed the best correlation with the cMRI values (r = 0.91, p < 0.001) and was similar to the mean cMRI value (49.6 ± 16 %, p not significant). Regional analysis showed a good correlation between both 8-frame and 16-frame QGS and cMRI wall motion score indexes (8-frame WMSI, r = 0.85; 16-frame WMSI, r = 0.89; p < 0.01). CONCLUSION: Low-dose gated SPECT with a CZT camera provides ventricular volumes that correlate well with cMRI results despite significant underestimation in the measure values. EF estimation appeared to be more accurate with 16-frame reformatted images than with 8-frame images.

Role of Imaging in Cardiomyopathies.

Imaging has a central role in the diagnosis, classification, and clinical management of cardiomyopathies. While echocardiography is the first-line technique, given its wide availability and safety, advanced imaging, including cardiovascular magnetic resonance (CMR), nuclear medicine and CT, is increasingly needed to refine the diagnosis or guide therapeutic decision-making. In selected cases, such as in transthyretin-related cardiac amyloidosis or in arrhythmogenic cardiomyopathy, the demonstration of histological features of the disease can be avoided when typical findings are observed at bone-tracer scintigraphy or CMR, respectively. Findings from imaging techniques should always be integrated with data from the clinical, electrocardiographic, biomarker, genetic and functional evaluation to pursue an individualised approach to patients with cardiomyopathy.

High diagnostic accuracy of low-dose gated-SPECT with solid-state ultrafast detectors: preliminary clinical results.

PURPOSE: Appropriate use of SPECT imaging is regulated by evidence-based guidelines and appropriateness criteria in an effort to limit the burden of radiation administered to patients. We aimed at establishing whether the use of a low dose for stress-rest single-day nuclear myocardial perfusion imaging on an ultrafast (UF) cardiac gamma camera using cadmium-zinc-telluride solid-state detectors could be used routinely with the same accuracy obtained with standard doses and conventional cameras. METHODS: To this purpose, 137 consecutive patients (mean age 61 ± 8 years) with known or suspected coronary artery disease (CAD) were enrolled. They underwent single-day low-dose stress-rest myocardial perfusion imaging using UF SPECT and invasive coronary angiography. Patients underwent the first scan with a 7-min acquisition time 10 min after the end of the stress protocol (dose range 185 to 222 MBq of (99m)Tc-tetrofosmin). The rest scan (dose range 370 to 444 MBq of (99m)Tc-tetrofosmin) was acquired with a 6-min acquisition time. The mean summed stress scores (SSS) and mean summed rest scores (SRS) were obtained semiquantitatively. RESULTS: Coronary angiograms showed significant epicardial CAD in 83% of patients. Mean SSS and SRS were 10 ± 5 and 3 ± 3, respectively. Overall the area under the ROC curve for the SSS values was 0.904, while the areas under the ROC curves for each vascular territory were 0.982 for the left anterior descending artery, 0.931 for the left circumflex artery and 0.889 for the right coronary artery. CONCLUSION: This pilot study demonstrated the feasibility of a low-dose single-day stress-rest fasting protocol performed using UF SPECT, with good sensitivity and specificity in detecting CAD at low patient exposure, opening new perspectives in the use of myocardial perfusion in ischaemic patients.

Evaluation of ischaemia in obese patients: feasibility and accuracy of a low-dose protocol with a cadmium-zinc telluride camera.

PURPOSE: Obesity is a significant and independent risk factor for cardiovascular disease, and assessing ischaemia in obese patients is clinically important but sometimes difficult because of imaging artefacts. The aim of this study was to evaluate the feasibility and diagnostic accuracy of stress/rest imaging with a cadmium-zinc telluride (CZT) camera using a low-dose protocol in a series of consecutive obese patients referred for the evaluation of coronary artery disease. METHODS: We considered 148 consecutive obese patients (mean BMI 39 ± 7 kg/m(2)) with known or suspected coronary artery disease referred to our laboratory for stress/rest myocardial perfusion imaging. A subgroup of 103 of the 148 patients underwent invasive coronary angiography for clinical reasons. All patients underwent a single-day stress/rest low-dose ultrafast protocol. Patients were injected with (99m)Tc-tetrofosmin at a dose in the range 185-222 MBq during bicycle exercise or dipyridamole stress, and underwent the first scan with an acquisition time of 7 min starting 15 min after the end of the stress. The rest scan with an acquisition time of 6 min was started from 30 to 45 min after (99m)Tc-tetrofosmin injection at a dose in the range 370-444 MBq. Images were visually inspected, and the summed stress score (SSS) and summed rest score (SRS) were obtained. RESULTS: Image quality was graded very good or excellent in all patients. Of the 103 patients who underwent coronary angiography, 12 (12 %), 26 (25 %) and 56 (54 %) showed one-, two- and three-vessel disease, and 9 showed normal coronary vessels. In the 103 patients submitted to coronary angiography, the mean SSS and SRS were 7 ± 6 and 2 ± 3, respectively. Semiquantitative regional and global SSS was a good discriminant of coronary artery disease and the area under the overall ROC curve was 0.848 (95 % CI 0.723-0.975). CONCLUSION: In obese patients, a single-day stress/rest low-dose ultrafast protocol with a CZT camera is clinically feasible and provides high image quality.

Combined Metabolically Active Tumor Volume and Early Metabolic Response Improve Outcome Prediction in Metastatic Colorectal Cancer.

Stratification of metastatic colorectal cancer (mCRC) patients is mostly based on clinical and biologic characteristics. This study aimed to validate the prognostic value of 18F-FDG PET/CT-based biomarkers such as baseline whole-body metabolically active tumor volume (WB-MATV) and early metabolic response (mR) in mCRC. Methods: The development cohort included chemorefractory mCRC patients enrolled in 2 prospective Belgian multicenter trials evaluating last-line treatments (multikinase inhibitors). The validation cohort included mCRC patients from an Italian center treated with chemotherapy and bevacizumab as first-line. Baseline WB-MATV was defined as the sum of metabolically active volumes of all target lesions identified on the baseline 18F-FDG PET/CT. Early mR assessment was performed following usual response criteria (response threshold of 30% [PERCIST-30%], response threshold of 15% [PERCIST-15%], European Organization for Research and Treatment of Cancer) and the so-called CONSIST method, which defines response as a decrease of SULmax ≥ 15% for all target lesions. Baseline WB-MATV and early mR assessment were investigated along with usual clinical factors and correlated with overall survival (OS) and progression-free survival (PFS). Results: Clinical factors, baseline WB-MATV, and early mR were evaluable in 192 of 239 and 94 of 125 patients of the development and validation cohorts, respectively. Except for PERCIST-30%, all response methods were equivalent in terms of outcome prediction, and CONSIST was found to be the most accurate. Baseline WB-MATV and early mR using the CONSIST method were independent prognostic parameters after adjustment for clinical factors in the development and validation sets for both OS (hazard ratio [HR] WB-MATV: 1.87 [95% CI, 1.17-2.97], P = 0.005, and HR early mR: 1.79 [95% CI, 1.08-2.95], P = 0.02 for the validation set) and PFS (HR WB-MATV: 1.94 [95% CI, 1.27-2.97], P = 0.002, and HR early mR: 1.69 [95% CI, 1.04-2.73], P = 0.03 for the validation set). Conclusion: Baseline WB-MATV and early mR are strong independent prognostic biomarkers for OS and PFS in mCRC, regardless of treatment received. Therefore, combining these biomarkers improves risk stratification for OS and PFS in mCRC.

Tissue Characterization in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) has long been considered a rare disease, but recent advancements in diagnostic tools have led to a reconsideration of the epidemiology of CA. Amyloid light-chain (AL) and transthyretin (ATTR) amyloidoses are the most common forms of cardiac amyloidosis. Due to the distinct treatments and the different prognoses, amyloid typing is crucial. Although a non-biopsy diagnosis can be obtained in ATTR amyloidosis when certain diagnostic criteria are fulfilled, tissue characterization still represents the gold standard for the diagnosis and typing of CA, particularly in AL amyloidosis. The present review focuses on the status of tissue characterization in cardiac amyloidosis, from histochemistry to immunohistochemistry and mass spectrometry, as well as on its future directions.

Impact of attenuation correction and gated acquisition in SPECT myocardial perfusion imaging: results of the multicentre SPAG (SPECT Attenuation Correction vs Gated) study.

PURPOSE: In clinical myocardial single photon emission computed tomography (SPECT), attenuation artefacts may cause a loss of specificity in the identification of diseased vessels that can be corrected by means of gated SPECT (GSPECT) acquisition or CT attenuation correction (AC). The purpose of this multicentre study was to assess the impact of GSPECT and AC on the diagnostic performance of myocardial scintigraphy, according to patient's sex, body mass index (BMI) and site of coronary artery disease (CAD). METHODS: We studied a group of 104 patients who underwent coronary angiography within 1 month before or after the SPECT study. Patients with a BMI>27 were considered "overweight". Attenuation-corrected and standard GSPECT early images were randomly interpreted by three readers blinded to the clinical data. RESULTS: In the whole group, GSPECT and AC showed a diagnostic accuracy of 86.5% (sensitivity 82%, specificity 93%) and 77% (sensitivity 75.4%, specificity 81.4%), respectively (p<0.05). In women, when anterior ischaemia was matched with CAD, AC failed to show any increase in specificity (AC 63.6% vs GSPECT 63.6%) with evident loss of sensitivity (AC 72.7% vs GSPECT 90.9%). AC significantly improved SPECT specificity in the identification of right CAD in overweight men (AC 100% vs GSPECT 66.7%, p<0.05). CONCLUSION: AC improved specificity in the evaluation of right CAD in overweight men. In the other evaluable subgroups specificity was not significantly affected while sensitivity was frequently reduced.

The Role of 18FDG PET/CT in the Assessment of Endocarditis, Myocarditis and Pericarditis.

Endocarditis, myocarditis and pericarditis are a heterogeneous group of phenotypic syndromes where the culprit area of inflammation is the heart. Inflammation may be determined by an infective agent, toxins, drugs or an activated immune system. Clinical manifestations can be subtle and diagnosis remains a challenge for cardiologists, requiring high level of suspicion and advanced multimodal cardiac imaging to avoid life-threatening consequences. The purpose of this review is to report the recent advances of PET/CT imaging with 18FDG in helping the management of patients affected by inflammatory heart disease. Two independent reviewers searched in PubMed articles published before or in June 2019 and final decisions on the inclusion of references were done in consensus with a third reviewer. At the end of the selection process 23/206 articles on "cardiac inflammation"; 26/235 articles on "endocarditis", "prosthetic heart valve", "pacemaker", "implantable cardiac device"; 7/103 articles on "myocarditis"; 13/330 articles on sarcoidosis" and 2/19 articles on "pericarditis" were included. Compared with the conventional methods, molecular imaging has the advantage to non-invasively and directly trace the inflammatory process, and to identify earlier the presence and the extent of intra-cardiac and extra-cardiac involvement, to enable quantification of disease activity, guide therapeutic interventions, and monitor treatment success.

Biopsy Evidence of Sequential Transthyretin and Immunoglobulin Light-Chain Cardiac Amyloidosis in the Same Patient.

Currently adopted diagnostic flow charts consider transthyretin and light-chain cardiac amyloidosis as mutually exclusive. Here, we report for the first time, to our knowledge, the demonstration of a biopsy-proven dual pathology in an 80-year-old man with sequential development of both wild-type transthyretin amyloidosis and light-chain cardiac amyloidosis cardiomyopathy over a 3-year timespan. (Level of Difficulty: Intermediate.).