Predicting adverse cardiac events in sarcoidosis: deep learning from automated characterization of regional myocardial remodeling.

Recognizing early cardiac sarcoidosis (CS) imaging phenotypes can help identify opportunities for effective treatment before irreversible myocardial pathology occurs. We aimed to characterize regional CS myocardial remodeling features correlating with future adverse cardiac events by coupling automated image processing and data analysis on cardiac magnetic resonance (CMR) imaging datasets. A deep convolutional neural network (DCNN) was used to process a CMR database of a 10-year cohort of 117 consecutive biopsy-proven sarcoidosis patients. The maximum relevance - minimum redundancy method was used to select the best subset of all the features-24 (from manual processing) and 232 (from automated processing) left ventricular (LV) structural/functional features. Three machine learning (ML) algorithms, logistic regression (LogR), support vector machine (SVM) and multi-layer neural networks (MLP), were used to build classifiers to categorize endpoints. Over a median follow-up of 41.8 (inter-quartile range 20.4-60.5) months, 35 sarcoidosis patients experienced a total of 43 cardiac events. After manual processing, LV ejection fraction (LVEF), late gadolinium enhancement, abnormal segmental wall motion, LV mass (LVM), LVMI index (LVMI), septal wall thickness, lateral wall thickness, relative wall thickness, and wall thickness of 9 (out of 17) individual LV segments were significantly different between patients with and without endpoints. After automated processing, LVEF, end-diastolic volume, end-systolic volume, LV mass and wall thickness of 92 (out of 216) individual LV segments were significantly different between patients with and without endpoints. To achieve the best predictive performance, ML algorithms selected lateral wall thickness, abnormal segmental wall motion, septal wall thickness, and increased wall thickness of 3 individual segments after manual image processing, and selected end-diastolic volume and 7 individual segments after automated image processing. LogR, SVM and MLP based on automated image processing consistently showed better predictive accuracies than those based on manual image processing. Automated image processing with a DCNN improves data resolution and regional CS myocardial remodeling pattern recognition, suggesting that a framework coupling automated image processing with data analysis can help clinical risk stratification.

Regional Myocardial Remodeling Characteristics Correlates With Cardiac Events in Sarcoidosis.

BACKGROUND: The poor prognosis of cardiac sarcoidosis (CS) underscores the need for risk stratification. PURPOSE: To investigate the prognostic significance of ventricular/myocardial remodeling features in sarcoidosis. STUDY TYPE: Retrospective. POPULATION: In all, 132 biopsy-proven sarcoidosis patients imaged from 2008 to 2018. The primary endpoint was a composite of cardiac mortality, new onset arrhythmias, hospitalization for heart failure, and device implantation. FIELD STRENGTH/SEQUENCE: No field strength or sequence restrictions. ASSESSMENT: Global and regional ventricular/myocardial remodeling features were assessed by standard volumetric measurements and automated function imaging postprocessing analysis. STATISTICAL TESTS: Student's t-test or Mann-Whitney test (chi2 test or Fisher's exact test for categorical variables) were used for comparisons. Cox-proportional hazards regression model, univariate /multivariate analyses, and receiver operating characteristic were performed to relate clinical/lab data, imaging parameters to the endpoints. RESULTS: Over a median follow-up of 40.7 (interquartile range 18.8-60.5) months, 41 (31.1%) patients developed adverse cardiac events. Abnormal left ventricular (LV) geometric remodeling alterations (measured by LV mass index and relative wall thickness) occurred 3.66-fold more frequently in patients with endpoints than patients without. The ratio of patients with endpoints increased as ventricular remodeling phenotype progressed. In patients with endpoints, regional myocardial wall thickness (RMWT) was significantly (P = 0.022) increased in six clustered LV segments located in the middle interventricular septum and basal/middle anterolateral walls. In all of the abnormal ventricular remodeling stages, patients with endpoints constantly had higher mean RMWT than those without. Among clinical, electrocardiographic, and imaging parameters, LV mass index (hazard ratio [HR] 1.010 95% confidence interval [CI] 1.002-1.018, P = 0.017) and mean RMWT (HR 3.482 95% CI 1.679-7.223, P = 0.001) were independently associated with endpoints. Sarcoidosis patients without this RMWT distribution pattern were significantly (P < 0.001) more likely to be free of the occurrence of subsequent cardiac events. DATA CONCLUSION: Regional myocardial remodeling characteristics are associated with subsequent adverse cardiac events in sarcoidosis. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:499-509.

Discrepant myocardial microvascular perfusion and mechanics after acute myocardial infarction: Characterization of the "Tako-tsubo effect" with real-time myocardial perfusion contrast echocardiograph.

BACKGROUND: In patients with acute anterior myocardial infarction (MI), sometimes an "apical ballooning" contractile dysfunction pattern that exceeds factual myocardial injury is identified in the ventriculography and bedside echocardiography. The hemodynamic consequences/sequela of this "Tako-tsobu effect" has not been well delineated. Of note, this anatomic imaging finding often misleads frontline physicians who assume reciprocal causation of persistent cardiac pump failure and ventricular pressure overload. METHODS AND RESULTS: Using real-time myocardial perfusion contrast echocardiography (MCE), we investigated myocardial (microvascular) perfusion in 60 patients after acute MI and coronary revascularization. Twenty-eight percent of the studied patients showed significantly mismatched myocardial perfusion and contractile defects. In these patients, an integrated imaging assessment with coronary angiography/ventriculography, deformation echocardiography, and MCE proved that the myocardial mechanic abnormalities significantly exceeded the defected perfusion areas. Compared with 72% of the patients without perfusion-contractility mismatch, apparently worse systolic functions (left ventricular ejection, wall motion score, and systolic longitudinal strain) in these patients did not change diastolic ventricular filling pressures (E/E' and E/A) or hemodynamic consequences/adverse events. Both systolic and diastolic functions in patients with perfusion-contractility mismatch appeared to be comparable with those in patients with Tako-tsubo syndrome. CONCLUSIONS: Real-time MCE identifies discrepant myocardial microvascular perfusion and mechanics in patients with acute MI. The "Tako-tsubo effect" in patients with perfusion-contractility mismatch does not cause diastolic filling pressure change or worse hemodynamic consequence/cardiac event.

Infimal convolution-based regularization for SPECT reconstruction.

PURPOSE: Total variation (TV) regularization is efficient in suppressing noise, but is known to suffer from staircase artifacts. The goal of this work was to develop a regularization method using the infimal convolution of the first- and the second-order derivatives to reduce or even prevent staircase artifacts in the reconstructed images, and to investigate if the advantage in noise suppression by this TV-type regularization can be translated into dose reduction. METHODS: In the present work, we introduce the infimal convolution of the first- and the second-order total variation (ICTV) as the regularization term in penalized maximum likelihood reconstruction. The preconditioned alternating projection algorithm (PAPA), previously developed by the authors of this article, was employed to produce the reconstruction. Using Monte Carlo-simulated data, we evaluate noise properties and lesion detectability in the reconstructed images and compare the results with conventional total variation (TV) and clinical EM-based methods with Gaussian post filter (GPF-EM). We also evaluate the quality of ICTV regularized images obtained for lower photon number data, compared with clinically used photon number, to verify the feasibility of radiation-dose reduction to patients by use of the ICTV reconstruction method. RESULTS: By comparison with GPF-EM reconstructed images, we have found that the ICTV-PAPA method can achieve a lower background variability level while maintaining the same level of contrast. Images reconstructed by the ICTV-PAPA method with 80,000 counts per view exhibit even higher channelized Hotelling observer (CHO) signal-to-noise ratio (SNR), as compared to images reconstructed by the GPF-EM method with 120,000 counts per view. CONCLUSIONS: In contrast to the TV-PAPA method, the ICTV-PAPA reconstruction method avoids substantial staircase artifacts, while producing reconstructed images with higher CHO SNR and comparable local spatial resolution. Simulation studies indicate that a 33% dose reduction is feasible by switching to the ICTV-PAPA method, compared with the GPF-EM clinical standard.

Mechanical interventricular dependency supports hemodynamics in tako-tsubo cardiomyopathy.

BACKGROUND: Although morphological abnormalities of the heart appear to be remarkable, most patients with tako-tsubo cardiomyopathy (TTC) remain clinically stable. We investigate real time changes in the left ventricular (LV) and right ventricular (RV) mechanics and function to explore the mechanism to preserve hemodynamics. METHODS: With deformation and Doppler echocardiography, we evaluated myocardial mechanics and ventricular function/hemodynamics simultaneously in 103 consecutive TTC patients admitted from 01/01/2008 through 12/31/2015. The coronary angiography and left ventriculography were performed to rule out culprit coronary artery stenosis (CAS). We included 66 patients in a control group with matched age, sex, and risk factors for coronary artery disease (CAD), and 41 patients in a group of myocardial infarction induced cardiogenic shock, who required circulatory supporting devices to maintain hemodynamic stability. RESULTS: Although systolic myocardial strain in most of the LV segments was significantly impaired, 4 basal LV segments remained functionally active during acute stage of TTC. The impairment in the myocardial strain of the RV apex could extend to the middle segments, but basal RV systolic strain was also preserved. Despites comparable apical to basal strain gradients, LV and RV displayed discrepant functional/hemodynamic status. In contrast to LV, RV functional/hemodynamic parameters appeared to be hyper-dynamic. This unique RV strain pattern remained unchanged in patients with atypical (mid-LV cavity) TTC. In 41 patients with myocardial infarction induced cardiogenic shock, RV exhibited comparable mechanic and functional features with those in TTC patients. CONCLUSIONS: The identified LV and RV mechanic changes appear to support interventricular hemodynamic dependence during TTC, which may represent a universal rescue mechanism in a jeopardized or injured heart.

Myocardial contractile patterns predict future cardiac events in sarcoidosis.

The poor prognosis of cardiac sarcoidosis (CS) underscores the need for risk stratification. We evaluated 84 consecutive sarcoidosis patients who were referred for echocardiographic studies for cardiac symptoms or abnormal electrocardiograms. In 54 patients without previous diagnosis of CS or other known structural heart disease, 13 reached endpoints during (median) 24 months follow up. Significantly impaired peak systolic longitudinal strain in their original echocardiograms were identified in 13 of 17 left ventricular segments, clustering in the free wall, interventricular septum and apex. The regional (including 13 clustered segments) peak systolic longitudinal strain (RPSLS) were significantly impaired in patients with endpoints, compared with those without [(-11.4 ± 4.45) vs. (-18.7 ± 3.76) %, P < 0.00001]. Cox multivariate regression analysis revealed that RPSLS was independently associated with endpoints (HR 1.24; 95% CI 1.08-1.42, P = 0.002). Receiver operating characteristic curve suggested a cut-off RPSLS value of -15.0% (84.6% sensitivity and 86.8% specificity) to predict the occurrence of endpoints. Impaired RPSLS correlates with risk of adverse cardiac events in patients with extra-cardiac sarcoidosis.

A 54-year-old man with new-onset ventricular fibrillation.

CLINICAL INTRODUCTION: A 54-year-old man without significant medical history presented with sudden-onset chest discomfort and multiple episodes of ventricular fibrillation requiring external defibrillation and cardiopulmonary resuscitation. Coronary angiography ruled out significant artery stenosis. Both ventriculography and echocardiography revealed decreased left ventricular ejection fraction (25%). On examination, he was haemodynamically stable. The lungs were clear to auscultation and there was no jugular venous dilation. The cardiac examination revealed a regular rate and rhythm without murmur. Cardiac magnetic resonance (CMR) and 18F-2-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) images were shown (figure 1).heartjnl;103/23/1922/F1F1F1Figure 1Cardiac magnetic resonance with a T1-weighted inversion recovery image (A) and 18F-2-fluoro-2-deoxyglucose positron emission tomography (B) in a 54-year-old man with new-onset ventricular fibrillation. QUESTION: Which of the following would be the next best step?Implantable loop recorderElectrophysiological testing for radiofrequency catheter ablationEndomyocardial biopsyGenetic testing.

Preconditioned alternating projection algorithm for solving the penalized-likelihood SPECT reconstruction problem.

PURPOSE: The authors recently developed a preconditioned alternating projection algorithm (PAPA) for solving the penalized-likelihood SPECT reconstruction problem. The proposed algorithm can solve a wide variety of non-differentiable optimization models. This work is dedicated to comparing the performance of PAPA with total variation (TV) regularization (TV-PAPA) and a novel forward-backward algorithm with nested expectation maximization (EM)-TV iteration scheme (FB-EM-TV). METHODS: Monte Carlo technique was used to simulate multiple noise realizations of the fan-beam collimated SPECT data for a piecewise constant phantom with warm background, and hot and cold spheres with uniform activities at two noise levels. They were reconstructed using the aforementioned algorithms with attenuation, scatter, distance-dependent collimator blurring and sensitivity corrections. Noise suppressing performance, lesion detectability, lesion contrast, contrast recovery coefficient, convergence speed and selection of optimal parameters were evaluated. The conventional EM algorithms with TV post-filter (TVPF-EM) and Gaussian post-filter (GPF-EM) were used as benchmarks. RESULTS: The TV-PAPA and FB-EM-TV demonstrated similar performance in all investigated categories. Both algorithms outperformed TVPF-EM in terms of image noise suppression, lesion detectability, lesion contrast and convergence speed. We established that the optimal parameters versus information density approximately followed power laws, which offers a guidance in parameter selection for reconstruction methods. CONCLUSIONS: For the simulated SPECT data, TV-PAPA and FB-EM-TV produced qualitatively and quantitatively similar images. They performed better than the benchmark TVPF-EM and GPF-EM, with only limited loss of lesion contrast.

Initial performance studies of a wearable brain positron emission tomography camera based on autonomous thin-film digital Geiger avalanche photodiode arrays.

Using analytical and Monte Carlo modeling, we explored performance of a lightweight wearable helmet-shaped brain positron emission tomography (PET), or BET camera, based on thin-film digital Geiger avalanche photodiode arrays with Lutetium-yttrium oxyorthosilicate (LYSO) or [Formula: see text] scintillators for imaging in vivo human brain function of freely moving and acting subjects. We investigated a spherical cap BET and cylindrical brain PET (CYL) geometries with 250-mm diameter. We also considered a clinical whole-body (WB) LYSO PET/CT scanner. The simulated energy resolutions were 10.8% (LYSO) and 3.3% ([Formula: see text]), and the coincidence window was set at 2 ns. The brain was simulated as a water sphere of uniform F-18 activity with a radius of 100 mm. We found that BET achieved [Formula: see text] better noise equivalent count (NEC) performance relative to the CYL and [Formula: see text] than WB. For 10-mm-thick [Formula: see text] equivalent mass systems, LYSO (7-mm thick) had [Formula: see text] higher NEC than [Formula: see text]. We found that [Formula: see text] scintillator crystals achieved [Formula: see text] full-width-half-maximum spatial resolution without parallax errors. Additionally, our simulations showed that LYSO generally outperformed [Formula: see text] for NEC unless the timing resolution for [Formula: see text] was considerably smaller than that presently used for LYSO, i.e., well below 300 ps.

Effective noise-suppressed and artifact-reduced reconstruction of SPECT data using a preconditioned alternating projection algorithm.

PURPOSE: The authors have recently developed a preconditioned alternating projection algorithm (PAPA) with total variation (TV) regularizer for solving the penalized-likelihood optimization model for single-photon emission computed tomography (SPECT) reconstruction. This algorithm belongs to a novel class of fixed-point proximity methods. The goal of this work is to investigate how PAPA performs while dealing with realistic noisy SPECT data, to compare its performance with more conventional methods, and to address issues with TV artifacts by proposing a novel form of the algorithm invoking high-order TV regularization, denoted as HOTV-PAPA, which has been explored and studied extensively in the present work. METHODS: Using Monte Carlo methods, the authors simulate noisy SPECT data from two water cylinders; one contains lumpy "warm" background and "hot" lesions of various sizes with Gaussian activity distribution, and the other is a reference cylinder without hot lesions. The authors study the performance of HOTV-PAPA and compare it with PAPA using first-order TV regularization (TV-PAPA), the Panin-Zeng-Gullberg one-step-late method with TV regularization (TV-OSL), and an expectation-maximization algorithm with Gaussian postfilter (GPF-EM). The authors select penalty-weights (hyperparameters) by qualitatively balancing the trade-off between resolution and image noise separately for TV-PAPA and TV-OSL. However, the authors arrived at the same penalty-weight value for both of them. The authors set the first penalty-weight in HOTV-PAPA equal to the optimal penalty-weight found for TV-PAPA. The second penalty-weight needed for HOTV-PAPA is tuned by balancing resolution and the severity of staircase artifacts. The authors adjust the Gaussian postfilter to approximately match the local point spread function of GPF-EM and HOTV-PAPA. The authors examine hot lesion detectability, study local spatial resolution, analyze background noise properties, estimate mean square errors (MSEs), and report the convergence speed and computation time. RESULTS: HOTV-PAPA yields the best signal-to-noise ratio, followed by TV-PAPA and TV-OSL/GPF-EM. The local spatial resolution of HOTV-PAPA is somewhat worse than that of TV-PAPA and TV-OSL. Images reconstructed using HOTV-PAPA have the lowest local noise power spectrum (LNPS) amplitudes, followed by TV-PAPA, TV-OSL, and GPF-EM. The LNPS peak of GPF-EM is shifted toward higher spatial frequencies than those for the three other methods. The PAPA-type methods exhibit much lower ensemble noise, ensemble voxel variance, and image roughness. HOTV-PAPA performs best in these categories. Whereas images reconstructed using both TV-PAPA and TV-OSL are degraded by severe staircase artifacts; HOTV-PAPA substantially reduces such artifacts. It also converges faster than the other three methods and exhibits the lowest overall reconstruction error level, as measured by MSE. CONCLUSIONS: For high-noise simulated SPECT data, HOTV-PAPA outperforms TV-PAPA, GPF-EM, and TV-OSL in terms of hot lesion detectability, noise suppression, MSE, and computational efficiency. Unlike TV-PAPA and TV-OSL, HOTV-PAPA does not create sizable staircase artifacts. Moreover, HOTV-PAPA effectively suppresses noise, with only limited loss of local spatial resolution. Of the four methods, HOTV-PAPA shows the best lesion detectability, thanks to its superior noise suppression. HOTV-PAPA shows promise for clinically useful reconstructions of low-dose SPECT data.

Electromagnetic effects on forearm disuse osteopenia: a randomized, double-blind, sham-controlled study.

A randomized, double-blind, sham-controlled, feasibility and dosing study was undertaken to determine if a common pulsing electromagnetic field (PEMF) treatment could moderate the substantial osteopenia that occurs after forearm disuse. Ninety-nine subjects were randomized into four groups after a distal radius fracture, or carpal surgery requiring immobilization in a cast. Active or identical sham PEMF transducers were worn on the distal forearm for 1, 2, or 4 h/day for 8 weeks starting after cast removal ("baseline") when bone density continues to decline. Bone mineral density (BMD) and bone geometry were measured in the distal forearm by dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) at entry ("baseline") and 8, 16, and 24 weeks later. Significant average BMD losses after baseline were observed in the affected forearm at all time points (5-7% distally and 3-4% for the radius/ulna shaft). However, after adjusting for age, gender, and baseline BMD there was no evidence of a positive effect of active versus sham PEMF treatment on bone loss by DXA or pQCT for subjects completing all visits (n = 82, ∼20 per group) and for an intent-to-treat analysis (n = 99). Regardless of PEMF exposure, serum bone-specific alkaline phosphatase (BSAP) was normal at baseline and 8 weeks, while serum c-terminal collagen teleopeptide (CTX-1) was markedly elevated at baseline and less so at 8 weeks. Although there was substantial variability in disuse osteopenia, these results suggested that the particular PEMF waveform and durations applied did not affect the continuing substantial disuse bone loss in these subjects.

What does PET imaging add to conventional staging of head and neck cancer patients?

PURPOSE: To determine the value of PET scans in the staging of patients with head and neck carcinoma. METHODS AND MATERIALS: The charts of 25 patients who underwent neck dissection, computed tomography (CT) scan, and F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging as part of their initial work-up for a head and neck squamous cell cancer between 2000-2003 were reviewed. All patients underwent clinical examination, triple endoscopy, and chest radiograph as part of their clinical staging, adhering to American Joint Commission for Cancer criteria. In addition to the clinical nodal (N) stage, PET findings were incorporated to determine a second type of N staging: clinical N + PET stage. The number of neck sides and nodal levels involved on CT or PET and on pathologic examination were recorded. RESULTS: The sensitivity and specificity for detection of nodal disease were similar for CT and FDG-PET. Positive and negative likelihood ratios were similar for both diagnostic tests. None of our 25 patients had unsuspected distant disease detected by PET. CONCLUSION: The addition of PET imaging did not improve diagnostic accuracy in our patients compared with CT. PET scanning did not alter clinical management in any of the patients.

MRI/PET nonrigid breast-image registration using skin fiducial markers.

We propose a finite-element method (FEM) deformable breast model that does not require elastic breast data for nonrigid PET/MRI breast image registration. The model is applicable only if the stress conditions in the imaged breast are virtually the same in PET and MRI. Under these conditions, the observed intermodality displacements are solely due the imaging/reconstruction process. Similar stress conditions are assured by use of an MRI breast-antenna replica for breast support during PET, and use of the same positioning. The tetrahedral volume and triangular surface elements are used to construct the FEM mesh from the MRI image. Our model requires a number of fiducial skin markers (FSM) visible in PET and MRI. The displacement vectors of FSMs are measured followed by the dense displacement field estimation by first distributing the displacement, vectors linearly over the breast surface and then distributing them throughout the volume. Finally, the floating MRI image is warped to a fixed PET image, by using an appropriate shape function in the interpolation from mesh nodes to voxels. We tested our model on an elastic breast phantom with simulated internal lesions and on a small number of patients imaged, with FMS using PET and MRI. Using simulated lesions (in phantom) and real lesions (in patients) visible in both PET and MRI, we established that the target registration error (TRE) is below two pet voxels.

Symptomatic and scintigraphic improvement after intravenous pamidronate treatment of Paget's disease of bone in patients with normal serum alkaline phosphatase levels.

OBJECTIVE: To describe three patients with symptomatic Paget's disease of bone who presented with normal levels of serum alkaline phosphatase. METHODS: We present three cases of Paget's disease of bone and chronicle the laboratory, scintigraphic, and clinical findings relative to treatment with intravenously administered pamidronate. RESULTS: Although measurement of serum total alkaline phosphatase usually provides a general indication of bone turnover in Paget's disease, about 15% of patients present with normal serum alkaline phosphatase levels. Nonetheless, these patients may have active Paget's disease when assessed with bone scintigraphy or urinary markers of bone resorption. All three study patients had xray findings characteristic of Paget's disease of bone, increased uptake of radiotracer material on bone scans, and elevated levels of urinary markers of bone resorption but normal alkaline phosphatase levels. They were treated with intravenously administered pamidronate, 60 mg once weekly for 2 to 3 consecutive weeks. After treatment, the serum alkaline phosphatase level decreased by 19 to 36%, markers of bone resorption normalized, bone scans showed improvement, and bone pain resolved. CONCLUSION: Pagetic activity in bone and related clinical manifestations may be present in the setting of a normal serum alkaline phosphatase level. Appropriate therapy should not be withheld because of the normal alkaline phosphatase.