Association between baseline hemodynamic indices, cardiotoxicity risk, and survival in women with breast cancer.

BACKGROUND: The outcome of breast cancer (BrCa) women monitored by low-dose equilibrium radionuclide angiography (ERNA) remains challenging to predict. AIM: This study aims to determine whether heart rate (HR)/blood pressure (BP) ratio-based indexes, previously confirmed to predict outcomes of various diseases, also predict BrCa-therapy-related cardiotoxicity and survival. METHODS: Predictors of cardiotoxicity and survival were determined among pre-therapy variables, including shock index ([SI HR/systolic BP) and age-adjusted SI (ASI), in a female BrCa cohort with normal baseline ERNA-left ventricular ejection fraction (LVEF). RESULTS: We included 274 women with a median age of 54.8 (interquartile range: 45.5-65.4) years, 271 treated with anthracyclines and 96 with trastuzumab. During a median follow-up of 25.9 (18.6-33.5) months, 31 women developed cardiotoxicity (LVEF: <50% and ≥10% drop from baseline), and 25 died. Baseline ASI was a multivariate predictor (p < 0.001) of (i) cardiotoxicity, in association with trastuzumab treatment (p = 0.010), and LV end-diastolic volume (p = 0.001) and (ii) survival, in association with metastasis (p < 0.001) and estimated glomerular filtration rate (p = 0.008). Cardiotoxicity poorly impacted survival (p = 0.064). The 36-month cardiotoxicity and mortality rates were markedly higher for patients in the upper half of baseline ASI values (ASI: >30 years min-1.mmHg-1, 16.5% and 20.7%, respectively) than in the lower half (7.6% and 4.5%, respectively, both p < 0.05). CONCLUSIONS: In BrCa women with normal baseline ERNA-LVEF, HR/BP ratio-based indexes unmask hemodynamic profiles associated with increased cardiotoxicity risk and decreased survival, highlighting the need for a comprehensive assessment of cardiac- and vascular-related risks in BrCa women monitored by ERNA. CONDENSED ABSTRACT: In a cohort of 274 women BrCa women who were monitored by ERNA for potentially cardiotoxic drugs (anthracyclines or trastuzumab) and who had no history of cardiac disease and a normal left ventricular ejection fraction before treatment, baseline indexes based on HR/BP ratios unmask hemodynamic profiles strongly associated with an increased risk of cardiotoxicity and subsequently decreased survival. Although further validations in other cohorts are needed, these findings highlight the need for a more comprehensive assessment of the cardiac- and vascular-related risk in BrCa women monitored by ERNA.

Routine first-line detection of breast cancer therapy-related cardiotoxicity by serial, fast and ultra-low-dose equilibrium radionuclide angiography.

BACKGROUND: This study assesses a first-line left ventricular ejection fraction (LVEF) monitoring provided by an ultra-low-dose equilibrium radionuclide angiography (ERNA) in breast cancer women treated with potentially cardiotoxic drugs and analyzes patient outcome based on the ERNA results. METHODS: Breast cancer women treated with anthracyclines, followed or not by trastuzumab, were monitored using ERNA with a high-sensitivity CZT-camera. Calibrated LVEF measurements were obtained with an almost threefold reduction of radiation doses and 10-min recording times. RESULTS: During a mean 24 ± 6 months follow-up, 552 ERNAs with a mean effective dose of 2.3 ± 0.6 mSv were performed in 195 women, among whom 22 (11%) presented both ERNA criteria of cardiotoxicity (LVEF < 50% and > 10% drop from baseline; Tox + group), 35 (18%) only one criterion (Tox ± group), and 138 (71%) neither (Tox - group). This ERNA-based classification correlated with trastuzumab-anthracycline treatment (p = 0.001), prior cardiovascular disease (p = 0.018), and cardiac outcome, with a 30-month survival with no cardiotoxicity-driven drug regimen changes of 97 ± 2% in Tox -, 60 ± 13% in Tox ± and 36 ± 13% in Tox + (p < 0.001) groups. CONCLUSION: First-line detection of breast cancer therapy-related cardiotoxicity by ultra-low-dose ERNA provides consistent results, confirming the excellent cardiac outcome for the greatest majority of women with no ERNA cardiotoxicity criteria.

Assessment of the routine reporting of very low-dose exercise-first myocardial perfusion SPECT from a large-scale real-world cohort and correlation with the subsequent reporting of coronary stenosis at angiography.

PURPOSE: Our study assesses the routine reporting of exercise ischemia using very low-dose exercise-first myocardial perfusion SPECT in a large number of patients and under real-life conditions, by evaluating correlations with the subsequent routine reporting of coronary stenosis by angiography and with factors that predict ischemia. METHODS: Data from 13,126 routine exercise MPI reports, from 11,952 patients (31% women), using very low doses of sestamibi and a high-sensitivity cardiac CZT camera, were extracted to assess the reporting of significant MPI-ischemia (> 1 left ventricular segment), to determine the MPI normalcy rate in a group with < 5% pretest probability of coronary artery disease (CAD) (n = 378), and to assess the ability of MPI to predict a > 50% coronary stenosis in patients with available coronary angiography reports in the 3 months after the MPI (n = 713). RESULTS: The median effective patient dose was 2.51 [IQR: 1.00-4.71] mSv. The normalcy rate was 98%, and the MPI-ischemia rate was independently predicted by a known CAD, the male gender, obesity, and a < 50% LV ejection fraction, ranging from 29.5% with all these risk factors represented to 1.5% when there were no risk factors. A > 50% coronary stenosis was significantly predicted by MPI-ischemia, less significantly for mild (odds ratio [95% confidence interval]: 1.61 [1.26-1.96]) than for moderate-to-severe MPI-ischemia (4.05 [3.53-4.57]) and was also impacted by having a known CAD (2.17 [1.83-2.51]), by a submaximal exercise test (1.48 [1.15-1.81]) and being ≥ 65 years of age (1.43 [1.11-1.76]). CONCLUSION: Ischemia detected using a very low-dose exercise-first MPI protocol in a large-scale clinical cohort and under real-life routine conditions is a highly significant predictor for the subsequent reporting of coronary stenosis, although this prediction is enhanced by other variables. This weakly irradiating approach is amenable to being repeated at shorter time intervals, in target patient groups with a high probability of MPI-ischemia.

Early 18F-FDG PET Flare-up Phenomenon After CAR T-Cell Therapy in Lymphoma.

ABSTRACT: 18F-FDG PET/CT imaging series were acquired on a 64-year-old woman with refractory diffuse large B lymphoma to monitor chimeric antigen receptor (CAR) T-cell therapy. Because of a clinical deterioration, 18F-FDG PET/CT performed 8 days after CAR T-cell therapy suggested an early flare-up phenomenon with new lymph node involvement, lymph node progression while a decrease in metabolic tumor volume. The 18F-FDG PET/CT 1 month after CAR T-cell therapy confirmed this hypothesis. Pseudoprogression in solid tumors treated by immunotherapy has generally been reported later after treatment.

Strong Electron-Phonon Interaction in 2D Vertical Homovalent III-V Singularities.

Highly polar materials are usually preferred over weakly polar ones to study strong electron-phonon interactions and its fascinating properties. Here, we report on the achievement of simultaneous confinement of charge carriers and phonons at the vicinity of a 2D vertical homovalent singularity (antiphase boundary, APB) in an (In,Ga)P/SiGe/Si sample. The impact of the electron-phonon interaction on the photoluminescence processes is then clarified by combining transmission electron microscopy, X-ray diffraction, ab initio calculations, Raman spectroscopy, and photoluminescence experiments. 2D localization and layer group symmetry properties of homovalent electronic states and phonons are studied by first-principles methods, leading to the prediction of a type-II band alignment between the APB and the surrounding semiconductor matrix. A Huang-Rhys factor of 8 is finally experimentally determined for the APB emission line, underlining that a large and unusually strong electron-phonon coupling can be achieved by 2D vertical quantum confinement in an undoped III-V semiconductor. This work extends the concept of an electron-phonon interaction to 2D vertically buried III-V homovalent nano-objects and therefore provides different approaches for material designs, vertical carrier transport, heterostructure design on silicon, and device applications with weakly polar semiconductors.

Direct measurement of the spectral dependence of Lamb coupling constant in a dual frequency quantum well-based VECSEL.

Spectral dependence of Lamb coupling constant C is experimentally investigated in an InGaAlAs Quantum Wells active medium. An Optically-Pumped Vertical-External-Cavity Surface-Emitting Laser is designed to sustain the oscillation of two orthogonally polarized modes sharing the same active region while separated in the rest of the cavity. This laser design enables to tune independently the two wavelengths and, at the same time, to apply differential losses in order to extract without any extrapolation the actual coupling constant. C is found to be almost constant and equal to 0.84 ± 0.02 for frequency differences between the two eigenmodes ranging from 45 GHz up to 1.35 THz.

Head-to-head comparison of image quality between brain 18F-FDG images recorded with a fully digital versus a last-generation analog PET camera.

BACKGROUND: The quality of phantom images was previously shown to be higher on digital (Vereos Philips®) compared to analog PET (Ingenuity Philips®) cameras. This study aimed to determine the extent to which this difference still remains significant on normal brain 18F-FDG PET images. METHODS: Relative noise and contrast as well as border sharpness (a spatial resolution index) of central (striata) and peripheral (occiput) gray-matter structures were compared between 10 sets of normal brain 18F-FDG PET images recorded and reconstructed on digital and analog last-generation PET cameras, together with a subjective visual analysis of image quality provided by experienced physicians. RESULTS: Compared with analog PET, digital PET provided marked improvements in image quality parameters. The median relative noise was decreased (- 22%), while gray/white-matter contrast was increased (+ 27%/+ 41% for central/peripheral gray-matter structures), with these results being consistent with visual analysis. In addition, a clear enhancement in image sharpness was further documented for digital PET owing to the possible use of a 1-mm3 voxel size (+ 24%/+ 21%). CONCLUSIONS: On normal brain 18F-FDG images and compared with a last-generation analog PET, the fully digital PET camera offers marked improvements in image noise and contrast, as well as significant potential for further enhancing spatial resolution.

Left ventricular ejection fraction determined with the simulation of a very low-dose CZT-SPECT protocol and an additional count-calibration on planar radionuclide angiographic data.

PURPOSE: To determine whether the left ventricular ejection fractions (EFs), measured on a high-sensitivity CZT single photon emission computed tomography (SPECT)-camera with a 70% reduction in recording times and a prevention of EF overestimation through an additional count-calibration, are concordant with reference EF from planar radionuclide angiography (2D-RNA). METHODS: An additional 10-minute CZT-SPECT recording was performed in patients referred to 2D-RNA for cardiomyopathy (n = 23) or chemotherapy monitoring (n = 50) with an in vivo red blood cell labeling with 850 MBq [Formula: see text]. The EF, obtained from CZT-SPECT with 100% (SPECT100) or 30% (SPECT30) projection times and with a SPECT-count calibration on the 2D-RNA counts of corresponding cavity volumes, were compared to EF from 2D-RNA. RESULTS: Strong and equivalent relationships were documented between the EF from 2D-RNA and the calibrated EF from SPECT100 (y = 0.89x + 6.62; R2 = 0.87) and SPECT30 (y = 0.87x + 8.40; R2 = 0.85), and the mean EF from SPECT100 (54% ± 15%) and SPECT30 (53% ± 16%) were close to that from 2D-RNA (55% ± 15%). However, upward shifts in these mean values were documented in the absence of count calibration for both SPECT100 (60% ± 18%) and SPECT30 (60% ± 18%). CONCLUSION: Left ventricular EF may be determined on a high-sensitivity CZT-camera, a 70% reduction in injected activities, and an additional count-calibration for further enhancing the concordance with 2D-RNA values.

High-Resolution Brain 18F-FDG Images Provided by Fully Digital PET.

Normal brain F-FDG PET images, consecutively recorded on analog and fully digital PET cameras in an 85-year-old woman, are depicted herein with the reconstruction methods recommended for a 2-mm voxel size on each camera and with a high-resolution reconstruction additionally developed for digital PET with a 1-mm voxel size. An enhanced gray-to-white matter contrast was consistently documented for digital PET when compared with analog PET, and was associated with a further enhancement in spatial resolution at 1-mm voxel size, as evidenced by a much clearer delineation of cortical gyri. These high-resolution images could favor the identification of brain abnormalities.

Assessment of Myocardial CZT SPECT Recording in a Forward-Leaning Bikerlike Position.

This prospective randomized study assessed myocardial perfusion imaging with the high-sensitivity D.SPECT cadmium-zinc-telluride camera in a forward-leaning bikerlike position, which may potentially lower diaphragmatic attenuation and reduce breathing-related cardiac motion, in a manner comparable to the prone position proposed with other SPECT cameras. Methods: Patients referred for a stress-rest 99mTc-sestamibi protocol and positioned in the biker position, with the chest leaning forward on the D.SPECT camera-head at 35° from vertical, had an additional resting D.SPECT recording in the supine position (n = 40) or in the sitting position with the back rearward at 30° from vertical (n = 40). Segments with attenuation artifacts were defined as those with less than 65% uptake but with strictly normal contractility at gated SPECT and no defect reversibility from stress images. Results: The biker position was associated with lower heart-to-detector distances than the supine or sitting positions (both P < 0.001); lower cardiac motion amplitudes, assessed on panograms, than the supine position (P < 0.001); and fewer segments with attenuation artifacts than the supine position (on average, 1.10 ± 1.01 vs. 1.90 ± 1.74, P = 0.010) or the sitting position (0.75 ± 0.93 vs. 1.38 ± 1.60, P = 0.011). Conclusion: Myocardial perfusion images from D.SPECT are enhanced for patients positioned in a forward-leaning bikerlike position comparatively to sitting or supine positions, with a notably lower rate of attenuation artifacts.

Central Nervous System Myelomatosis Delineated by High-Resolution Brain Images From Fully Digital 18F-FDG PET.

Central nervous system myelomatosis is uncommon and is associated with a particularly poor prognosis. PET images, from a 53-year-old man referred to a fully digital F-FDG PET for relapsed multiple myeloma, revealed high F-FDG uptakes located in the cortex and sulci of the right central area and within the meningeal envelopes of the cerebellum, the trigeminal nerves, and on the spinal canal. These particular uptakes gave evidence of a central nervous system myelomatosis subsequently confirmed by plasma cells documented in cerebrospinal fluid. Such interesting images could be obtained owing to the potential of high-resolution images provided by fully digital F-FDG PET.

Routine evaluation of left ventricular function using CZT-SPECT, with low injected activities and limited recording times.

PURPOSE: Gamma-cameras, with Cadmium-Zinc-Telluride (CZT) detectors, allow to perform myocardial perfusion imaging (MPI) with limited injected activities and recorded times. This study aimed at determining whether the routine assessment of left ventricular (LV) function with such limited counts protocols compares well with reference values from cardiac MRI. METHODS: The study included patients who have undergone cardiac MRI and an MPI routinely planned on a CZT camera with a low-dose protocol (120 MBq of Sestamibi for stress and 360 MBq at rest for 75 kg body weight), while targeting the recording of only 500 myocardial kcounts in order to limit the recording times (<10 minutes for stress, <4 minutes for rest). SPECT images were reconstructed with a method maintaining rather high spatial (8 mm) and temporal (16 frames/cycle) resolutions. RESULTS: Seventy-six patients were included, and mean effective dose was 3.5 ± 1.7 mSv for the total MPI protocol. Correlations between CZT-SPECT and MRI were good to excellent for ejection fraction (r 2 = 0.77), end-diastolic (r 2 = 0.88) and end-systolic (r 2 = 0.93) volumes, and the analysis of segmental contractility correlated well between the two techniques (kappa score = 0.72 ± 0.02). CONCLUSION: LV function, assessed on a CZT camera with low injected activities and limited recording times, correlates well with the reference assessment from cardiac MRI.

Low-dose dual-isotope procedure planed for myocardial perfusion CZT-SPECT and assessed through a head-to-head comparison with a conventional single-isotope protocol.

PURPOSE OF THE REPORT: This study aimed at assessing an original low-dose dual-isotope procedure in which the abnormal stress Tc-99m Sestamibi SPECT is followed by rest Tl-201 SPECT, along with a head-to-head comparison with a single-isotope procedure. METHODS AND RESULTS: One hundred two patients, referred for a low-dose stress-SPECT with Sestamibi (123 ± 20 MBq) on a CZT camera and for whom a rest Sestamibi SPECT was warranted, had an additional Tl-201 rest-SPECT (52 ± 5 MBq) between stress and rest Sestamibi SPECT recordings. Tl-201 images were processed for spill-over and scatter corrections, and uptake differences with stress Sestamibi SPECT were analyzed: (1) for rest acquisitions from Tl-201 (dual-isotope procedure) and from Sestamibi (single-isotope procedure) and (2) in segments for which a diagnosis of ischemia, infarct, or normal perfusion was achieved. Mean effective dose was 8.3 mSv for dual-isotope but would decrease to 5.7 mSv for an expected rate of 37% of patients for whom rest-SPECT is not warranted. After a further background correction of Tl-201 images, the rest-stress difference in myocardial uptake was equivalent between dual- and single-procedures for identifying ischemic segments (respective areas-under-curves: 0.83 ± 0.03 and 0.81 ± 0.03). CONCLUSION: This original dual-isotope procedure provides acceptable radiation doses and consistent results, as compared with conventional single-isotope.

Aneurysmal angiosarcoma associated with vascular graft revealed by 18F-FDG-PET imaging.

We report a rare case of vascular graft-associated aneurysmal angiosarcoma by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). An 81-year-old male patient, with a prior history of graft interposition 1 year previously, was referred to 18F-FDG-PET because of an inflammatory syndrome of unknown origin. FDG-PET images revealed a particular pattern of intense circular uptake within the arterial wall (SUVmax = 10) in a popliteal aneurysm and, additionally, a large hypermetabolic mass centered by the graft. Remote hypermetabolisms in lung nodules and pleural thickenings were also detected. The diagnosis of angiosarcoma was ascertained through histopathological analysis of surgical samples. Development of an aneurysmal angiosarcoma at the site of a vascular graft is a rare entity, often misdiagnosed. 18F-FDG-PET appears to be useful in its detection with a PET pattern of intense circular uptake within the arterial wall. Such finding should lead to the search for distant metastasis.

Central pulse pressure is a determinant of heart and brain remodeling in the elderly: a quantitative MRI and PET pilot study.

OBJECTIVE: The sustained elevation of blood pressure (BP) and especially of central pulse pressure (cPP) leads to heart and brain damage. This pilot study was aimed to precise the relationships between peripheral and central BP levels, and the remodeling of heart and brain as objectively quantified by cardiac MRI and brain F-fluorodeoxyglucose (FDG)-PET imaging in the elderly. METHODS: Twenty-eight apparently healthy elderly individuals (66-85 years old, 14 women) were prospectively recruited and allocated into two half groups, one with and one without hypertension, and all were referred for the quantitative determinations of peripheral and central BP using applanation tonometry, indexed left ventricular mass (per m of body surface area) using cardiac MRI, and brain metabolism with a voxel-based analysis of FDG-PET images adjusted for age and sex. RESULTS: Indexed left ventricular mass, reflecting cardiac remodeling, was correlated with the overall pressure variables involving both peripheral and central levels of systolic and pulse pressure (all P ≤ 0.001). By contrast, brain metabolism was significantly correlated with only cPP (P < 0.02). A cPP of at least 50  mmHg was associated with both a lower metabolism in frontal areas (P = 0.005) and a higher indexed left ventricular mass (P = 0.03). CONCLUSION: This pilot study suggests that, when quantified by MRI and PET imaging, left ventricular mass and brain metabolism of elderly individuals are related to the cPP and to the 50  mmHg threshold, corresponding to what has previously been documented for the risk of cardiovascular event.

Stress-first protocol for myocardial perfusion SPECT imaging with semiconductor cameras: high diagnostic performances with significant reduction in patient radiation doses.

PURPOSE: Effective doses of 14 mSv or higher are currently being attained in patients having stress and rest myocardial perfusion imaging (MPI) single photon emission computed tomography (SPECT) performed on the same day with conventional protocols. This study aimed to assess the actual reduction in effective doses as well as diagnostic performances for MPI routinely planned with: (1) high-sensitivity cadmium zinc telluride (CZT) cameras, (2) very low injected activities and (3) a stress-first protocol where the normality of stress images may lead to avoiding rest imaging. METHODS: During a 1-year period, 2,845 patients had MPI on a CZT camera, a single-day stress-first protocol and low injected activities (120 MBq of (99m)Tc-sestamibi at stress for 75 kg body weight and threefold higher at rest). The ability to detect > 50% coronary stenosis was assessed in a subgroup of 149 patients who also had coronary angiography, while the normalcy rate was assessed in a subgroup of 128 patients with a low pretest likelihood of coronary artery disease (<10%). RESULTS: Overall, 33% of patients had abnormal MPI of which 34% were women and 34% were obese. The mean effective doses and the percentage of exams involving only stress images were: (1) 3.53 ± 2.10 mSv and 37% in the overall population, (2) 4.83 ± 1.56 mSv and 5% in the subgroup with angiography and (3) 1.96 ± 1.52 mSv and 71 % in the low-probability subgroup. Sensitivity and global accuracy for identifying the 106 patients with coronary stenosis were 88 and 80%, respectively, while the normalcy rate was 97 %. CONCLUSION: When planned with a low-dose stress-first protocol on a CZT camera, MPI provides high diagnostic performances and a dramatic reduction in patient radiation doses. This reduction is even greater in low-risk subgroups with high rates of normal stress images, thus allowing the mean radiation dose to be balanced against cardiac risk in targeted populations.

Theoretical and experimental studies of (In,Ga)As/GaP quantum dots.

(In,Ga)As/GaP(001) quantum dots (QDs) are grown by molecular beam epitaxy and studied both theoretically and experimentally. The electronic band structure is simulated using a combination of k·p and tight-binding models. These calculations predict an indirect to direct crossover with the In content and the size of the QDs. The optical properties are then studied in a low-In-content range through photoluminescence and time-resolved photoluminescence experiments. It suggests the proximity of two optical transitions of indirect and direct types.