[18F]-florbetaben PET/CT is sensitive for cardiac AL amyloidosis.

Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients.

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.

Wild-type transthyretin cardiac amyloidosis is not rare in elderly subjects: the CATCH screening study.

AIMS: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) affects older adults and is currently considered as a rare disorder. We investigated for the first time the prevalence of ATTRwt-CA in elderly individuals from the general population. METHODS AND RESULTS: General practitioners from Pisa, Italy, proposed a screening for ATTRwt-CA to all their patients aged 65-90 years, until 1000 accepted. The following red flags were searched: interventricular septal thickness ≥ 12 mm, any echocardiographic, electrocardiographic 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. Four patients received a non-invasive diagnosis of ATTRwt-CA. All complained of dyspnoea 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 and 3 diastolic dysfunction, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 1000 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). CONCLUSION: Wild-type transthyretin cardiac amyloidosis 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. Wild-type transthyretin cardiac amyloidosis is considered a rare disease, although no systematic screening has been performed yet. The study aimed to understand how common this disease is among the general population aged 65­90 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 1000 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.

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.

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.

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.

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.

Amyloid Deposits and Fibrosis on Left Ventricular Endomyocardial Biopsy Correlate With Extracellular Volume in Cardiac Amyloidosis.

Background The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. Methods and Results We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68-81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%-30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%-23%; range, 5%-60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. Conclusions Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone.

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.).

Deep-learning-based cardiac amyloidosis classification from early acquired pet images.

The objective of the present work was to evaluate the potential of deep learning tools for characterizing the presence of cardiac amyloidosis from early acquired PET images, i.e. 15 min after [18F]-Florbetaben tracer injection. 47 subjects were included in the study: 13 patients with transthyretin-related amyloidosis cardiac amyloidosis (ATTR-CA), 15 patients with immunoglobulin light-chain amyloidosis (AL-CA), and 19 control-patients (CTRL). [18F]-Florbetaben PET/CT images were acquired in list mode and data was sorted into a sinogram, covering a time interval of 5 min starting 15 min after the injection. The resulting sinogram was reconstructed using OSEM iterative algorithm. A deep convolutional neural network (CAclassNet) was designed and implemented, consisting of five 2D convolutional layers, three fully connected layers and a final classifier returning AL, ATTR and CTRL scores. A total of 1107 2D images (375 from AL-subtype patients, 312 from ATTR-subtype, and 420 from Controls) have been considered in the study and used to train, validate and test the proposed network. CAclassNet cross-validation resulted with train error mean ± sd of 2.001% ± 0.96%, validation error of 4.5% ± 2.26%, and net accuracy of 95.49% ± 2.26%. Network test error resulted in a mean ± sd values of 10.73% ± 0.76%. Sensitivity, specificity, and accuracy evaluated on the test dataset were respectively for AL-CA sub-type: 1, 0.912, 0.936; for ATTR-CA: 0.935, 0.897, 0.972; for control subjects: 0.809, 0.971, 0.909. In conclusion, the proposed CAclassNet model seems very promising as an aid for the clinician in the diagnosis of CA from cardiac [18F]-Florbetaben PET images acquired a few minutes after the injection.

[18F]-Florbetaben PET/CT for Differential Diagnosis Among Cardiac Immunoglobulin Light Chain, Transthyretin Amyloidosis, and Mimicking Conditions.

OBJECTIVES: This study aimed to test the diagnostic value of [18F]-florbetaben positron emission tomography (PET) in patients with suspicion of CA. BACKGROUND: Diagnosis of cardiac involvement in immunoglobulin light-chain-derived amyloidosis (AL) and transthyretin-related amyloidosis (ATTR), which holds major importance in risk stratification and decision making, is frequently delayed. Furthermore, although diphosphonate radiotracers allow a noninvasive diagnosis of ATTR, demonstration of cardiac amyloidosis (CA) in AL may require endomyocardial biopsy. METHODS: Forty patients with biopsy-proven diagnoses of CA (20 ALs, 20 ATTRs) and 20 patients referred with the initial clinical suspicion and later diagnosed with non-CA pathology underwent a cardiac PET/computed tomography scan with a 60-min dynamic [18F]-florbetaben PET acquisition, and 4 10-min static scans at 5, 30, 50, and 110 min after radiotracer injection. RESULTS: Visual qualitative assessment showed intense early cardiac uptake in all subsets. Patients with AL displayed a high, persistent cardiac uptake in all the static scans, whereas patients with ATTR and those with non-CA showed an uptake decrease soon after the early scan. Semiquantitative assessment demonstrated higher mean standardized uptake value (SUVmean) in patients with AL, sustained over the whole acquisition period (early SUVmean: 5.55; interquartile range [IQR]: 4.00 to 7.43; vs. delayed SUVmean: 3.50; IQR: 2.32 to 6.10; p = NS) compared with in patients with ATTR (early SUVmean: 2.55; IQR: 1.80 to 2.97; vs. delayed SUVmean: 1.25; IQR: 0.90 to 1.60; p < 0.001) and in patients with non-CA (early SUVmean: 3.50; IQR: 1.60 to 3.37; vs. delayed SUVmean: 1.40; IQR: 1.20 to 1.60; p < 0.001). Similar results were found comparing heart-to-background ratio and molecular volume. CONCLUSIONS: Delayed [18F]-florbetaben cardiac uptake may discriminate CA due to AL from either ATTR or other mimicking conditions. [18F]-florbetaben PET/computed tomography may represent a promising noninvasive tool for the diagnosis of AL amyloidosis, which is still often challenging and delayed. (A Prospective Triple-Arm, Monocentric, Phase-II Explorative Study on Evaluation of Diagnostic Efficacy of the PET Tracer [18F]-Florbetaben [Neuraceq] in Patients With Cardiac Amyloidosis [FLORAMICAR2]; EudraCT number: 2017-001660-38).

Cardiac sympathetic denervation in wild-type transthyretin amyloidosis.

BACKGROUND: Tissue accumulation of misfolded transthyretin (TTR) may occur because of TTR gene mutations (variant amyloid TTR amyloidosis, ATTRv), or as an age-related phenomenon (wild-type ATTR, ATTRwt). Cardiac sympathetic denervation has been reported in ATTRv, but has never been investigated in ATTRwt. METHODS: Fifteen consecutive patients with ATTRwt cardiomyopathy (81% men, median age 82 years, no one with prior myocardial infarction) underwent Cadmium Zinc Telluride tomographic imaging for amyloid burden (99mTc-hydroxymethylene diphosphonate - 99mTc-HMDP), innervation (123I-metaiodobenzylguanidine - 123I-MIBG), and perfusion (99mTc-tetrofosmin). RESULTS: Median summed 99mTc-HMDP score was 60 (58-62), denoting a severe and diffuse amyloid burden. Planar 123I-MIBG examination showed decreased early and late H/M ratios (late H/M ratio: 1.5 [1.3-1.6], range 1.2-1.9, reference value ≥2.0). Summed 123I-MIBG score was 12 (6-22), with the most prominent denervation in the infero-septal, inferior, and infero-lateral regions; summed rest score was 7 (5-11), with lowest degrees of myocardial perfusion in the inferior and infero-septal regions. The correlation between amyloid burden (as relative 99mTc-HMDP uptake) and innervation (as relative 123I-MIBG uptake) did not achieve statistical significance at both segmental (p = .252) and regional level (p = .251). Nevertheless, denervation tended to worsen in parallel with the amyloid burden, and 123I-MIBG scores increased with 99mTc-HMDP scores. Segments and regions with prominent hypoperfusion also showed a higher degree of denervation (r = 0.500 and 0.591, respectively; both p < .001). CONCLUSIONS: Patients with ATTRwt cardiomyopathy display cardiac sympathetic denervation, particularly in the inferior and septal myocardial wall. Myocardial hypoperfusion has a similar regional pattern, while the amyloid burden is more extensive.

Diphosphonate single-photon emission computed tomography in cardiac transthyretin amyloidosis.

BACKGROUND: Planar diphosphonate scintigraphy is an established diagnostic tool for amyloid transthyretin (ATTR) cardiomyopathy. Characterization of the amyloid burden up to the segmental level by single photon emission computed tomography (SPECT) has not been evaluated so far. METHODS: Data from consecutive patients undergoing cardiac 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) SPECT and diagnosed with ATTR cardiomyopathy at a tertiary referral center from June 2016 to April 2019 were collected. RESULTS: Thirty-eight patients were included (median age 81 years, 79% men, 92% with wild-type ATTR). In patients with Perugini score 1, the most intense diphosphonate regional uptake was found in septal segments, particularly in infero-septal segments. Among patients scoring 2, the amyloid burden in the septum became more significant, and extended to inferior and apical segments. Finally, patients scoring 3 displayed an intense and widespread tracer uptake. All patients with Perugini score 1 had LGE in at least one antero-septal, one infero-septal, and one infero-lateral segment. All patients with score 2 displayed LGE in infero-septal, inferior, and infero-lateral segments. LGE became extensive in patients scoring 3, with all patients having at least one LGE-positive segment in each region. CONCLUSIONS: When assimilating different Perugini grades to evolutive stages of the disease, amyloid deposition seem to progress from the septum to the inferior wall and then to the other regions and from the basis to the apex. The potential of segmental analysis might be particularly relevant in patients with very limited cardiac uptake at planar scintigraphy (Perugini score 1).

Keys to early diagnosis of cardiac amyloidosis: red flags from clinical, laboratory and imaging findings.

Cardiac involvement in systemic amyloidosis, due either to immunoglobulin light-chain or transthyretin amyloidosis, influences clinical presentation and is a strong predictor of unfavourable outcome. Until recently considered as a rare, incurable disease, cardiac amyloidosis, is still mis/underdiagnosed, although treatments effective in improving patient survival are now available for both subtypes, including chemotherapy regimens for immunoglobulin light-chain amyloidosis and tetramer stabiliser for transthyretin amyloidosis. Achieving a timely diagnosis allows initiating life-saving therapies and requires the early recognition of clinical, laboratory and imaging signs of cardiac involvement, some of them may be apparent well before the disease becomes clinically manifest. Given the systemic nature of amyloidosis, a close interaction among experts in multiple specialties is also required, including cardiologists, nephrologists, haematologists, neurologists, radiologists, nuclear medicine specialists and internists. As an increased awareness about disease presentation is required to ameliorate diagnostic performance, we aim to provide the clinician with a guide to the screening and early diagnosis of cardiac amyloidosis, and to review the clinical, biohumoral and instrumental 'red flags' that should raise the suspicion of cardiac amyloidosis.

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.

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.

Prognostic Significance of 2-Deoxy-2-[18F]-Fluoro-D-Glucose PET/CT in Patients With Locally Advanced Esophageal Cancer Undergoing Neoadjuvant Chemoradiotherapy Before Surgery: A Nonparametric Approach.

To investigate the prognostic value of tumor metabolism measurements on serial 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography and computed tomography scans in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiotherapy. Forty-five patients (63 ±â€Š7 years, 6 female) treated with concomitant chemoradiotherapy before surgery were followed up for 24 ±â€Š18 months (range 4-71). Positron emission tomography and computed tomography scans were obtained within 1 week before the start (PET1) and 1 month after the completion of the treatment (PET2). Total body tumor metabolic activity was measured as the sum of the parameters: SUVmax, SUV corrected for lean body mass, and total lesion glycolysis (TLG40/50/70%). Then, delta values for the parameters between PET1 and PET2 were calculated and expressed as percentage of PET1 results. At the time of the analysis, 27 patients were dead and 18 were alive. There was no difference between the 2 groups in terms of age, sex, site of the disease, histology, and the presence/absence of linfonodal metastases (P = NS). Survival random forest analysis (20,000 trees) resulted in an estimate of error rate of 36%. The nonparametric approach identified ΔTLG40 as the most predictive factor of survival (relative importance 100%). Moreover, T (17%), N (5%), and M (5%) stage of the disease, cancer histology (11%), TLG70 (5%) at the end of chemioradioterapy, and ΔTLG(50-70) (17%-5%) were positively associated with patient outcome. The nonparametric analysis confirmed the prognostic importance of some clinical parameters, such as TNM stage and cancer histology. Moreover, ΔTLG resulted to be the most important factor in predicting outcome and should be considered in risk stratification of patients treated with neoadjuvant chemoradiotherapy.

Assessment of myocardial adrenergic innervation with a solid-state dedicated cardiac cadmium-zinc-telluride camera: first clinical experience.

AIMS: To investigate the relationships between regional adrenergic innervation heterogeneity, myocardial perfusion, and contractile function obtained by means of a low-dose imaging protocol with a cadmium-zinc-telluride (CZT) dedicated camera. METHODS: Twenty-eight patients with or without ischaemic heart disease underwent (123)I-metaiodobenzylguanidine (MIBG) planar scintigraphic and CZT early and delayed evaluations followed by (99m)Tc-tetrofosmin rest gated CZT with a single-day protocol. The heart-to-mediastinum ratio and the washout rate were computed from planar (123)I-MIBG images. The summed (123)I-MIBG defect scores (SS-MIBG) were semi-quantitatively assessed from CZT images. The summed rest score (SRS), summed motion score (SMS), and summed thickening score (STS) were quantitated from (99m)Tc-tetrofosmin images. RESULTS: Sixteen patients showed a depressed left ventricular systolic function [ejection fraction (EF)<50%]. They presented higher SRS (P = 0.007), SMS (P < 0.001), STS (P < 0.001), and early SS-MIBG (P = 0.007) values than those with normal contractile function. Interestingly, higher early SS-MIBG values, index of regional sympathetic innervation heterogeneity, clustered with more elevated SRS (P = 0.023), and more impaired measures of regional and global left ventricle systolic function, i.e. SMS (P = 0.046), STS (P = 0.014), and EF (P = 0.027). At multivariate analysis, a higher SRS (P = 0.039) remained the only independent predictor of more elevated early SS-MIBG values. In the 20 of 28 ischaemic patients, the correlations between early SS-MIBG and SMS (P = 0.017) and also STS (P = 0.036) were further confirmed. The effective dose of the investigation was 4.2 ± 0.72 mSv. CONCLUSIONS: An altered early SS-MIBG, assessed with a low-dose imaging protocol and a CZT cardiac camera, identifies patients with more impaired myocardial perfusion and contractile function.

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.