A convolutional neural network-based system for fully automatic segmentation of whole-body [68Ga]Ga-PSMA PET images in prostate cancer.

PURPOSE: The aim of this study was development and evaluation of a fully automated tool for the detection and segmentation of mPCa lesions in whole-body [68Ga]Ga-PSMA-11 PET scans by using a nnU-Net framework. METHODS: In this multicenter study, a cohort of 412 patients from three different center with all indication of PCa who underwent [68Ga]Ga-PSMA-11 PET/CT were enrolled. Two hundred cases of center 1 dataset were used for training the model. A fully 3D convolutional neural network (CNN) is proposed which is based on the self-configuring nnU-Net framework. A subset of center 1 dataset and cases of center 2 and center 3 were used for testing of model. The performance of the segmentation pipeline that was developed was evaluated by comparing the fully automatic segmentation mask with the manual segmentation of the corresponding internal and external test sets in three levels including patient-level scan classification, lesion-level detection, and voxel-level segmentation. In addition, for comparison of PET-derived quantitative biomarkers between automated and manual segmentation, whole-body PSMA tumor volume (PSMA-TV) and total lesions PSMA uptake (TL-PSMA) were calculated. RESULTS: In terms of patient-level classification, the model achieved an accuracy of 83%, sensitivity of 92%, PPV of 77%, and NPV of 91% for the internal testing set. For lesion-level detection, the model achieved an accuracy of 87-94%, sensitivity of 88-95%, PPV of 98-100%, and F1-score of 93-97% for all testing sets. For voxel-level segmentation, the automated method achieved average values of 65-70% for DSC, 72-79% for PPV, 53-58% for IoU, and 62-73% for sensitivity in all testing sets. In the evaluation of volumetric parameters, there was a strong correlation between the manual and automated measurements of PSMA-TV and TL-PSMA for all centers. CONCLUSIONS: The deep learning networks presented here offer promising solutions for automatically segmenting malignant lesions in prostate cancer patients using [68Ga]Ga-PSMA PET. These networks achieve a high level of accuracy in whole-body segmentation, as measured by the DSC and PPV at the voxel level. The resulting segmentations can be used for extraction of PET-derived quantitative biomarkers and utilized for treatment response assessment and radiomic studies.

Differential privacy preserved federated transfer learning for multi-institutional 68Ga-PET image artefact detection and disentanglement.

PURPOSE: Image artefacts continue to pose challenges in clinical molecular imaging, resulting in misdiagnoses, additional radiation doses to patients and financial costs. Mismatch and halo artefacts occur frequently in gallium-68 (68Ga)-labelled compounds whole-body PET/CT imaging. Correcting for these artefacts is not straightforward and requires algorithmic developments, given that conventional techniques have failed to address them adequately. In the current study, we employed differential privacy-preserving federated transfer learning (FTL) to manage clinical data sharing and tackle privacy issues for building centre-specific models that detect and correct artefacts present in PET images. METHODS: Altogether, 1413 patients with 68Ga prostate-specific membrane antigen (PSMA)/DOTA-TATE (TOC) PET/CT scans from 3 countries, including 8 different centres, were enrolled in this study. CT-based attenuation and scatter correction (CT-ASC) was used in all centres for quantitative PET reconstruction. Prior to model training, an experienced nuclear medicine physician reviewed all images to ensure the use of high-quality, artefact-free PET images (421 patients' images). A deep neural network (modified U2Net) was trained on 80% of the artefact-free PET images to utilize centre-based (CeBa), centralized (CeZe) and the proposed differential privacy FTL frameworks. Quantitative analysis was performed in 20% of the clean data (with no artefacts) in each centre. A panel of two nuclear medicine physicians conducted qualitative assessment of image quality, diagnostic confidence and image artefacts in 128 patients with artefacts (256 images for CT-ASC and FTL-ASC). RESULTS: The three approaches investigated in this study for 68Ga-PET imaging (CeBa, CeZe and FTL) resulted in a mean absolute error (MAE) of 0.42 ± 0.21 (CI 95%: 0.38 to 0.47), 0.32 ± 0.23 (CI 95%: 0.27 to 0.37) and 0.28 ± 0.15 (CI 95%: 0.25 to 0.31), respectively. Statistical analysis using the Wilcoxon test revealed significant differences between the three approaches, with FTL outperforming CeBa and CeZe (p-value < 0.05) in the clean test set. The qualitative assessment demonstrated that FTL-ASC significantly improved image quality and diagnostic confidence and decreased image artefacts, compared to CT-ASC in 68Ga-PET imaging. In addition, mismatch and halo artefacts were successfully detected and disentangled in the chest, abdomen and pelvic regions in 68Ga-PET imaging. CONCLUSION: The proposed approach benefits from using large datasets from multiple centres while preserving patient privacy. Qualitative assessment by nuclear medicine physicians showed that the proposed model correctly addressed two main challenging artefacts in 68Ga-PET imaging. This technique could be integrated in the clinic for 68Ga-PET imaging artefact detection and disentanglement using multicentric heterogeneous datasets.

The effects of carvedilol, metoprolol and propranolol on cisplatin-induced kidney injury.

The ß-adrenoceptor blockers may have anti-oxidant properties or induce ß-arrestin recruitment beyond classical desensitization of receptor/G protein coupling, offering potential therapeutic benefits. Here, we investigated the effects of carvedilol, metoprolol and propranolol in an animal model of cisplatin-induced nephrotoxicity. Rats received the ß-blockers (3 or 12 mg/kg/day) with or without cisplatin, and kidney function was investigated using renal scintigraphy, histopathology, and serum variables. Metoprolol and propranolol as well as low-dose carvedilol did not alter kidney function, per se. Meanwhile, high-dose carvedilol reduced renal accumulation of Technetium-99m (99mTc)-labeled dimercaptosuccinic acid (99mTc-DMSA) without significant effect on other variables. Furthermore, low-dose carvedilol prevented cisplatin-induced reduction of tracer uptake, but high-dose of this drug aggravated the situation. In this regard, both low and high -doses of carvedilol significantly inhibited cisplatin effects on kidney histology, BUN and creatinine levels. Also, high-dose propranolol inhibited cisplatin adverse effects on radiotracer uptake, histological manifestations, BUN and creatinine levels, while metoprolol failed to cause a notable effect. Taken together, carvedilol and high-dose propranolol may offer potential benefits in cisplatin nephrotoxicity.

Diltiazem-loaded electrospun nanofibers as a new wound dressing: fabrication, characterization, and experimental wound healing.

Calcium channel blockers such as diltiazem have recently been investigated for their wound-healing potential. The aims of this study were to fabricate diltiazem-loaded nanofibers for a new wound dressing and investigate their beneficial properties for wound healing. Nanofibers were electrospun using polyvinyl alcohol solution containing 0, 2 or 4% diltiazem. Fibers were characterized in terms of physicochemical properties, drug release and fibroblast viability, and in animal wound healing assays. Compared to other formulations, nanofibers containing 4% diltiazem showed thin fiber size (152.7 nm), high porosity (88.4%), high swelling (110.4%), low water contact angle (29.1°) and little weight loss (17.3%). Drug release from 4%-diltiazem nanofibers showed good fit to a Korsmeyer-Peppas model, suggesting a non-Fickian release mechanism (R 2 = 96%, n = 0.52). In vitro, 4%-diltiazem mats were not cytotoxic and enhanced fibroblast proliferation by 263% after 5 days of treatment compared to control. In vivo, wounds treated with this mat for 14 days showed the smallest size (14.7%) and better histopathologic characteristics compared to other wounds. The 4%-diltiazem mat also demonstrated significant antioxidant activity by reducing tissue MDA and nitrite levels by 63 and 59% compared to normal saline. The findings support the eligibility of this novel wound dressing for additional clinical research.

The need for standardization of nuclear cardiology reporting and data system (NCAD-RADS): Learning from coronary artery disease (CAD), breast imaging (BI), liver imaging (LI), and prostate imaging (PI) RADS.

Newer structured reporting manners, the reporting and data system (RADS), have made vast steps in improving standardized and structured reporting, allowing better communication between radiologists and referring providers. This has been implemented in several fields: breast (BI-RADS), lung (Lung-RADS), liver (LI-RADS), thyroid (TI-RADS), prostate (PI-RADS), and in cardiovascular radiology (CAD-RADS). The field of nuclear cardiology began its efforts of standardization years ago; however, a widespread standardized reporting structure has not yet been adopted. Such an approach in nuclear cardiology, the nuclear cardiology reporting and data system (NCAD-RADS), will assist radiologists and treating clinicians in conveying and understanding reports and determining the appropriate next steps in management. By linking explicit findings to defined recommendations, patients will receive more consistent and appropriate care.

Comparison of 99mTc-DMSA renal scintigraphy with biochemical and histopathological findings in animal models of acute kidney injury.

Biochemical and histological assays are currently used for the diagnosis and characterization of kidney injury. The purpose of this study was to compare technetium-99m-labeled dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy, as a non-invasive method, with common biochemical and histopathological methods in two animal models of acute kidney injury. Nephrotoxicity was induced either by gentamicin (100 mg/kg/day for one week) or unilateral ureteral ligation (UUO). Renal scintigraphy was performed 1 h after intravenous injection of 99mTc-DMSA (3 mCi). Furthermore, plasma levels of blood urea nitrogen (BUN), creatinine, sodium, and potassium were determined using an autoanalyzer. At the end of experiments, kidneys were excised for the measurement of activity uptake (mCi/gr) using a dose calibrator as well as histopathological examinations with hematoxylin and eosin (H&E) staining. There was a significant decrease in 99mTc-DMSA uptake in both gentamicin (P value = 0.049) and UUO (P value = 0.034) groups, and it was more significant in the former. The levels of BUN and creatinine increased in both gentamicin and UUO groups, while the levels of sodium and potassium remained unchanged. Furthermore, a strong correlation was found between DMSA uptake and histopathological findings. Scintigraphy with 99mTc-DMSA is capable of detection of kidney injury in both gentamicin and UUO groups. Moreover, a significant correlation was found between scintigraphy parameters and histopathological findings. This suggests 99mTc-DMSA as a non-invasive method for the evaluation of kidney injury induced by drugs or anatomical disorders.

The correlation between insulin-like growth factor 1 (IGF-1) and novel adipocytokines in postmenopausal women: A population-based study.

The adipocytokines and insulin-like growth factor 1 (IGF-1) are involved in insulin resistance, the cardiometabolic syndrome, and atherosclerosis. Therefore, investigating the relationship between circulating levels of the novel adipocytokines and IGF-1 is worthwhile. The correlation between IGF-1, visfatin, and omentin-1 has not been adequately investigated. In a population-based study, 324 postmenopausal women were randomly selected. Circulating IGF-1, visfatin, omentin-1, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) levels were measured with the highly specific enzyme-linked immunosorbent assay method. In multiple regression analyses adjusted for alkaline phosphatase, osteocalcin, and hs-CRP, circulating IGF-1 was significantly correlated with visfatin levels (standardized ß coefficient [ß] = 0.13, partial correlation coefficient [r] = 0.12, p = 0.028). The significant positive correlation between serum IGF-1 and visfatin levels remained after additional adjustments for age and BMI (ß = 0.12, r = 0.12, p = 0.025), metabolic syndrome (ß = 0.13, r = 0.12, p = 0.021), and type 2 diabetes mellitus (ß = 0.13, r = 0.12, p = 0.026). No significant correlations were found between IGF-1, adiponectin, and omentin-1. There is a significant correlation between serum IGF-1 and visfatin levels in postmenopausal women beyond metabolic syndrome, type 2 diabetes, bone formation markers, and hs-CRP levels. The observed correlation between higher circulating IGF-1 and the higher visfatin levels might be a physiological compensation and adaptation to protect against visfatin-induced proinflammatory effects.

Implementation of absolute quantification in small-animal SPECT imaging: Phantom and animal studies.

PURPOSE: Presence of photon attenuation severely challenges quantitative accuracy in single-photon emission computed tomography (SPECT) imaging. Subsequently, various attenuation correction methods have been developed to compensate for this degradation. The present study aims to implement an attenuation correction method and then to evaluate quantification accuracy of attenuation correction in small-animal SPECT imaging. METHODS: Images were reconstructed using an iterative reconstruction method based on the maximum-likelihood expectation maximization (MLEM) algorithm including resolution recovery. This was implemented in our designed dedicated small-animal SPECT (HiReSPECT) system. For accurate quantification, the voxel values were converted to activity concentration via a calculated calibration factor. An attenuation correction algorithm was developed based on the first-order Chang's method. Both phantom study and experimental measurements with four rats were used in order to validate the proposed method. RESULTS: The phantom experiments showed that the error of -15.5% in the estimation of activity concentration in a uniform region was reduced to +5.1% when attenuation correction was applied. For in vivo studies, the average quantitative error of -22.8 ± 6.3% (ranging from -31.2% to -14.8%) in the uncorrected images was reduced to +3.5 ± 6.7% (ranging from -6.7 to +9.8%) after applying attenuation correction. CONCLUSION: The results indicate that the proposed attenuation correction algorithm based on the first-order Chang's method, as implemented in our dedicated small-animal SPECT system, significantly improves accuracy of the quantitative analysis as well as the absolute quantification.

Chlamydia pneumoniae and Helicobacter pylori IgG seropositivities are not predictors of osteoporosis-associated bone loss: a prospective cohort study.

The potential link between infection with Chlamydia pneumoniae or Helicobacter pylori and osteoporosis has not been investigated in population-based longitudinal studies. A total of 250 healthy postmenopausal women who participated in a prospective cohort study were evaluated for IgG antibodies directed against C. pneumoniae and H. p ylori, osteoprotegerin (OPG), the receptor activator of nuclear factor kappa B ligand (RANKL), CrossLaps, and osteocalcin. Bone mineral density (BMD) was measured at the femoral neck and lumbar spine at baseline and at follow-up 5.8 years later. There were no significant differences in age-adjusted bone turnover markers, OPG, RANKL, the RANKL/OPG ratio, and BMD between the C. p neumoniae and H. p ylori IgG seropositive and seronegative subjects (P > 0.05). Neither C. p neumoniae nor H. p ylori IgG seropositivity was associated with age-and body mass index-adjusted BMD at the femoral neck and lumbar spine or bone loss at the 5.8-year follow-up. In logistic regression analysis, neither C. p neumoniae nor H. p ylori IgG seropositivities predicted incident lumbar or spine osteoporosis 5.8 years later. In conclusion, neither C. p neumoniae nor H. p ylori IgG seropositivity was associated with bone turnover markers, the RANKL/OPG ratio, BMD, or bone loss in postmenopausal women. In addition, chronic infection with C. p neumoniae or H. p ylori did not predict incident osteoporosis among this group of women.

Brain perfusion imaging with voxel-based analysis in secondary progressive multiple sclerosis patients with a moderate to severe stage of disease: a boon for the workforce.

BACKGROUND: The present study was carried out to evaluate cerebral perfusion in multiple sclerosis (MS) patients with a moderate to severe stage of disease. Some patients underwent hyperbaric oxygen therapy (HBOT) and brain perfusion between before and after that was compared. METHODS: We retrospectively reviewed 25 secondary progressive (SP)-MS patients from the hospital database. Neurological disability evaluated by Expanded Disability Status Scale Score (EDSS). Brain perfusion was performed by (99 m) Tc-labeled bicisate (ECD) brain SPECT and the data were compared using statistical parametric mapping (SPM). In total, 16 patients underwent HBOT. Before HBOT and at the end of 20 sessions of oxygen treatment, 99mTc-ECD brain perfusion single photon emission computed tomography (SPECT) was performed again then the results were evaluated and compared. Brain perfusion was performed by (99 m) Tc-labeled bicisate (ECD) brain SPECT and the data were compared using statistical parametric mapping (SPM). RESULTS: A total of 25 SP-MS patients, 14 females (56 %) and 11 males (44 %) with a mean age of 38.92 ± 11.28 years included in the study. The mean disease duration was 8.70 ± 5.30 years. Of the 25 patients, 2 (8 %) had a normal SPECT and 23 (92 %) had abnormal brain perfusion SPECT studies. The study showed a significant association between severity of perfusion impairment with disease duration and also with EDSS (P <0.05). There was a significant improvement in pre- and post-treatment perfusion scans (P <0.05), but this did not demonstrate a significant improvement in the clinical subjective and objective evaluation of patients (P >0.05). CONCLUSIONS: This study depicted decreased cerebral perfusion in SP-MS patients with a moderate to severe disability score and its association with clinical parameters. Because of its accessibility, rather low price, practical ease, and being objective quantitative information, brain perfusion SPECT can be complementing to other diagnostic modalities such as MRI and clinical examinations in disease surveillance and monitoring. The literature on this important issue is extremely scarce, and follow up studies are required to assess these preliminary results.

OMENTIN-1 AND NONFATAL ISCHEMIC HEART DISEASE IN POSTMENOPAUSAL WOMEN: A POPULATION-BASED STUDY.

OBJECTIVE: There is growing evidence that supports the existence of a link between lower levels of circulating omentin-1 and the pathogenesis of coronary atherosclerosis. However, no population-based study has been performed to elucidate the cardioprotective role of this beneficial adipocytokine. METHODS: A total of 378 healthy, postmenopausal women were randomly selected from 13 clusters in the port city of Bushehr, Iran. The prevalence of nonfatal ischemic heart disease (IHD) was assessed using the Minnesota code with a 12-lead resting electrocardiogram (EKG). EKG with evidence of IHD (IHD-EKG) was defined as myocardial infarction (codes 1.1 and 1.2) and ischemia (codes 1.3, 4.1 to 4.4, 5.1 to 5.3, and 7.1) occurring together. Serum omentin-1 and adiponectin levels were measured using enzyme-linked immunosorbent assay methods. RESULTS: The prevalence of IHD-EKG among the studied population was 41.8% (159 women). Serum levels of omentin-1 were significantly lower in women with ischemic EKG than in normal subjects (geometric mean ×/multiplicative standard deviation, 10.31 ×/2.35 ng/mL versus 12.44 ×/2.12 ng/mL, respectively; P = .038). Multiple logistic regression analysis indicated that higher serum levels of omentin-1 were significantly associated with a lower prevalence of ischemic EKG after adjusting for potential confounders, including classical cardiovascular risk factors and circulating adiponectin levels (odds ratio, 0.48; confidence interval, 0.24 to 0.95; P = .038). CONCLUSION: A higher level of circulating omentin-1 is independently associated with a lower prevalence of nonfatal IHD in postmenopausal women. The cardioprotective role of this novel adipocytokine needs to be further elucidated in large-scale longitudinal studies. ABBREVIATIONS: BMI = body mass index EKG = electrocardiogram ELISA = enzyme-linked immunosorbent assay HDL = high-density lipoprotein IHD = ischemic heart disease LDL = low-density lipoprotein.

Is there a relationship between non-obstructive coronary artery disease or cardiac syndrome X and migraine? An integrated multi-disciplinary approach.

Non-obstructive coronary artery disease (CAD) which is mostly called cardiac syndrome X (CSX) is noted in about 30% of men and 40%-60% of women and seems to be incremental. In addition, frequent myocardial perfusion defects with various levels of severity are often seen in this disease. Recently, we noticed that the frequency of migraine in patients with CSX was noticeably higher than in healthy people and in CAD patients. This may support the evolving story that CSX is related to migraine and to chest pain and that CSX and migraine may have a similar pathophysiology. Hence, myocardial perfusion imaging could be used as a complement any diagnostic test to support the relation between CSX and migraine.

Optimization of paclitaxel-loaded poly (d,l-lactide-co-glycolide-N-p-maleimido benzoic hydrazide) nanoparticles size using artificial neural networks.

The aim of this study was to find a model using artificial neural networks (ANNs) to predict PLGA-PMBH nanoparticles (NPs) size in preparation by modified nanoprecipitation. The input variables were polymer content, drug content, power of sonication and ratio of organic/aqueous phase (i.e. acetone/water), while the NPs size of PLGA-PMBH was assumed as the output variable. Forty samples of PLGA-PMBH NPs containing anticancer drug (i.e. paclitaxel) were synthesized by changing the variable factors in the experiments. The data modeling were performed using ANNs. The effects of input variables (namely, polymer content, drug content, power of sonication and ratio of acetone/water) on the output variables were evaluated using the 3D graphs obtained after modeling. Contrasting the 3D graphs from the generated model revealed that the amount of polymer (PLGA-PMBH) and drug content (PTX) have direct relation with the size of polymeric NPs in the process. In addition, it was illustrated that the ratio of acetone/water was the most important factor affecting the particle size of PLGA-PMBH NPs provided by solvent evaporation technique. Also, it was found that increasing the sonication power (up to a certain amount) indirectly affects the polymeric NPs size however it was directly affected in higher values.

Size Control in the Nanoprecipitation Process of Stable Iodine (¹²7I) Using Microchannel Reactor-Optimization by Artificial Neural Networks.

In this study, nanosuspension of stable iodine ((127)I) was prepared by nanoprecipitation process in microfluidic devices. Then, size of particles was optimized using artificial neural networks (ANNs) modeling. The size of prepared particles was evaluated by dynamic light scattering. The response surfaces obtained from ANNs model illustrated the determining effect of input variables (solvent and antisolvent flow rate, surfactant concentration, and solvent temperature) on the output variable (nanoparticle size). Comparing the 3D graphs revealed that solvent and antisolvent flow rate had reverse relation with size of nanoparticles. Also, those graphs indicated that the solvent temperature at low values had an indirect relation with size of stable iodine ((127)I) nanoparticles, while at the high values, a direct relation was observed. In addition, it was found that the effect of surfactant concentration on particle size in the nanosuspension of stable iodine ((127)I) was depended on the solvent temperature. Nanoprecipitation process of stable iodine (127I) and optimization of particle size using ANNs modeling.

Hepatobiliary scintigraphy with SPET in the diagnosis of bronchobiliary fistula due to a hydatid cyst.

In this report, we present the application of hepatobiliary scintigraphy using Tc-99m mebrofenin in the diagnosis of bronchobiliary fistula caused by a liver hydatid cyst, which penetrated the diaphragm. Hepatobiliary scintigraphy noticeably depicted the leakage of the tracer from the biliary system of the liver to the bronchial tree. Hepatobiliary scintigraphy stands as a robust modality in the accurate diagnosis and treatment planning of bronchobiliary fistulas.

Technetium-99m-ubiquicidin scintigraphy in the detection of infective endocarditis.

We present a case of infective endocarditis (IE) diagnosed by the increased (99m)Tc-UBI specific uptake in the tricuspid valve region. In conclusion, our case data may indicate a first pass-like distribution with strong avidity of the tracer to infective endocarditis, facilitating image interpretation.

Bone mineral density is not related to angiographically diagnosed coronary artery disease.

Based on data, there may exist an association between low bone mineral density (BMD) and atherosclerosis. This study aimed to investigate the association between BMD and coronary artery disease (CAD). In this study the possible association of BMD with CAD in 65 men with CAD and in 49 men with normal angiography as well as in 51 women with CAD and in 51 normal women was investigated. Both spinal and femoral BMD values for men were higher than those of women (P<0.05). Neither femoral nor spinal BMD values were different in patients with or without CAD. In addition, BMD values were not associated with the severity of CAD. Body mass index (BMI) was positively correlated with BMD both in men and women, whereas age and anti-diabetic treatment were linked with lower BMD in women. In conclusion, in this study CAD was not related to low BMD. However, BMI was an independent predictor of diminished BMD.

The effects of Ramadan fasting on the health and function of the eye.

BACKGROUND: Ramadan fasting may alter a variety of physiological parameters which by themselves influence ocular system. Here, we review the effects of Ramadan fasting on the health and function of the eye. MATERIALS AND METHODS: Literature records in PubMed/MEDLINE, Web of Science, EMBASE, Google Scholar, and Iran Medex databases as well as proceedings of related meetings from January 1986 to March 2014 were systematically reviewed. The search key words was based on the terms "Ramadan Fasting," "Ramadan," "Islamic Fasting," "Fasting in Ramadan" accompanied with one of the eye, tear drop, myopia, intraocular pressure (IOP), tear break up time, basal tear secretion, refractive error, and visual acuity. RESULTS: Predawn water loading and dehydration in the evening are shown to increase and decrease IOP and tear secretion, respectively. Ocular blood flow is changed in Ramadan fasting, and patients with ocular vein occlusion may experience more frequent attacks. There are no or minimal fluctuations in visual acuity and refractive errors, but most of them are decompensated after Ramadan. CONCLUSION: Although the influence of fasting in different eye parameters is evaluated in several studies, there are no or only limited studies conducted on patients suffering from glaucoma, damage to ophthalmic vasculature, tear dysfunction, and minimal visual acuity. Such studies are required to make a definite decision before fasting is declared harmless to these patients.