SSELM-neg: spherical search-based extreme learning machine for drug-target interaction prediction.

BACKGROUND: The experimental verification of a drug discovery process is expensive and time-consuming. Therefore, efficiently and effectively identifying drug-target interactions (DTIs) has been the focus of research. At present, many machine learning algorithms are used for predicting DTIs. The key idea is to train the classifier using an existing DTI to predict a new or unknown DTI. However, there are various challenges, such as class imbalance and the parameter optimization of many classifiers, that need to be solved before an optimal DTI model is developed. METHODS: In this study, we propose a framework called SSELM-neg for DTI prediction, in which we use a screening approach to choose high-quality negative samples and a spherical search approach to optimize the parameters of the extreme learning machine. RESULTS: The results demonstrated that the proposed technique outperformed other state-of-the-art methods in 10-fold cross-validation experiments in terms of the area under the receiver operating characteristic curve (0.986, 0.993, 0.988, and 0.969) and AUPR (0.982, 0.991, 0.982, and 0.946) for the enzyme dataset, G-protein coupled receptor dataset, ion channel dataset, and nuclear receptor dataset, respectively. CONCLUSION: The screening approach produced high-quality negative samples with the same number of positive samples, which solved the class imbalance problem. We optimized an extreme learning machine using a spherical search approach to identify DTIs. Therefore, our models performed better than other state-of-the-art methods.

Vimentin and tumor-stroma ratio for neoadjuvant chemoradiotherapy response prediction in locally advanced rectal cancer.

Vimentin expression in tumor tissues and the tumor-stroma ratio (TSR) have been demonstrated as strong prognostic factors for cancer patients, but whether they are predictive markers of neoadjuvant chemoradiotherapy (nCRT) outcome in locally advanced rectal cancer (LARC) patients is poorly understood. This study aimed to explore the predictive significance of vimentin and TSR combined for nCRT response in LARC patients. Imaging mass cytometry (IMC) was performed to determine the association of vimentin and TSR with nCRT response in six LARC patients [three achieved pathological complete response (pCR), three did not]. Immunohistochemistry (IHC) for vimentin and TSR on biopsy tissues before nCRT and logistic regression analysis were performed to further evaluate their predictive value for treatment responses in a larger patient cohort. A trend of decreased vimentin expression and increased TSR in the pCR group was revealed by IMC. In the validation group, vimentin [odds ratio (OR) 0.260, 95% confidence interval (CI) 0.102-0.602, p = 0.002] and TSR (OR 4.971, 95% CI 1.933-15.431, p = 0.002) were associated with pCR by univariate analysis. Patients in the vimentin-low/TSR-low or vimentin-high/TSR-high (OR 5.211, 95% CI 1.248-35.582, p = 0.042) and vimentin-low/TSR-high groups (OR 11.846, 95% CI 3.197-77.079, p = 0.001) had significantly higher odds of pCR. By multivariate analysis, only the combination of vimentin and TSR was an independent predictor for nCRT response (OR 9.324, 95% CI 2.290-63.623, p = 0.006). Our study suggested that the combined assessment of vimentin and TSR can provide additive significance and may be a promising indicator of nCRT response in LARC patients.

Effect of Imaging Markers on Reperfusion Therapy in Basilar Artery Occlusion.

OBJECTIVE: We aimed to investigate the effectiveness of endovascular therapy (EVT) versus intravenous thrombolysis (IVT) in patients with basilar artery occlusion (BAO), based on the information of advanced imaging. METHODS: We analyzed data of stroke patients with radiologically confirmed BAO within 24 hours. BAO subjects were categorized into "top-of-the-basilar" syndrome (TOBS) and other types. An initial infarct size of <70ml and a ratio of ischemic tissue to infarct volume of ≥1.8 was defined as "target mismatch." The primary outcome was a good outcome, defined as a modified Rankin Scale score of 0 to 3 at 3 months. Propensity score adjustment and inverse probability of treatment weighting (IPTW) propensity score methods were used. RESULTS: Among 474 BAO patients, 93 (19.6%) were treated with IVT prior to EVT, 91 (19.2%) were treated with IVT alone, 95 (20.0%) were treated with EVT alone, and 195 (41.1%) were treated with antithrombotic therapy. In IPTW analyses, we found no benefit of EVT over IVT for good outcome in either TOBS patients (odds ratio = 1.08, 95% confidence interval [CI] = 0.88-1.31) or those with other types (odds ratio = 1.13, 95% CI = 0.94-1.36). However, in patients with other types, if there existed a target mismatch, EVT was independently related to good outcome (odds ratio = 1.46, 95% CI = 1.17-1.81). INTERPRETATION: The "target mismatch profile" seems to be a possible candidate selection standard of EVT for those with other types of BAO. Future studies should separate TOBS from other types of BAO, and try to use advanced imaging. ANN NEUROL 2022;92:97-106.

A two-stage cardiac PET and late gadolinium enhancement MRI co-registration method for improved assessment of non-ischemic cardiomyopathies using integrated PET/MR.

PURPOSE: Respiratory motion causes mismatches between PET images of the myocardium and the corresponding cardiac MR images in cardiac integrated PET/MR. The mismatch may affect the attenuation correction and the diagnosis of non-ischemic cardiomyopathies. In this study, we present a two-stage cardiac PET and MR late gadolinium enhancement (LGE) co-registration method, which seeks to improve diagnostic accuracy of non-ischemic cardiomyopathies via better image co-registration using an integrated whole-body PET/MR system. METHODS: The proposed PET and LGE two-stage co-registration method was evaluated through comparison with one-stage direct co-registration and no-registration. One hundred and ninety-one slices of LGE and forty lesions were studied. Two trained nuclear medicine physicians independently assessed the displacement between LGE and PET to qualitatively evaluate the co-registration quality. The changes of the mean SUV in the normal myocardium and the LGE-enhanced lesions before and after image co-registration were measured to quantitatively evaluate the accuracy and value of image co-registration. RESULTS: The two-stage method had an improved image registration score (4.93 ± 0.89) compared with the no-registration method (3.49 ± 0.84, p value < 0.001) and the single-stage method (4.23 ± 0.81, p value < 0.001). Furthermore, the two-stage method led to increased SUV value in the myocardium (3.87 ± 2.56) compared with the no-registration method (3.14 ± 1.92, p value < 0.001) and the single-stage method (3.32 ± 2.16, p value < 0.001). The mean SUV in the LGE lesion significantly increased from 2.51 ± 2.09 to 2.85 ± 2.35 (p value < 0.001) after the two-stage co-registration. CONCLUSION: The proposed two-stage registration method significantly improved the co-registration between PET and LGE in integrated PET/MR imaging. The technique may improve diagnostic accuracy of non-ischemic cardiomyopathies via better image co-registration. REGISTERED NO: DF-2020-085,2020.04.30.

ASF1B enhances migration and invasion of lung cancers cell via regulating the P53-mediated epithelial-mesenchymal transformation (EMT) signaling pathway.

Lung cancer is one of the most common malignant tumors in the world. Anti-silencing function 1B (ASF1B) has been demonstrated to play crucial roles in various tumors. However, the function of ASF1B in lung cancer remains to be addressed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays demonstrated that ASF1B expression was upregulated in human lung cancer tissues and cells. High expression of ASF1B in lung cancer patients was associated with tumor stage and lymph node metastatic status and indicated a poor prognosis. The results of CCK-8 and colony formation assays indicated that ASF1B promoted the proliferation of lung cancer cells. Moreover, ASF1B knockdown suppressed xenograft tumor growth and inhibited the levels of ASF1B and Ki-67. Transwell assay demonstrated that ASF1B promoted the migration and invasion of lung cancer cells. Importantly, mechanism analysis implied that upregulation of ASF1B decreased the expression of P53 and P21 while increasing the expression of Snail and Slug. Consistently, the knockdown of ASF1B led to the opposite results. Notably, P53 activation with Nutlin3 significantly weakened the epithelial-mesenchymal transformation (EMT) promotion effect of ASF1B, while P53 inhibition with pifithrin-α significantly enhanced the EMT promotion effect of sh-ASF1B. These data indicated that ASF1B exerts its oncogene function partially through the P53-mediated EMT signaling pathway. In conclusion, ASF1B promotes cell proliferation, migration, and invasion through modulating the P53-mediated EMT signaling pathway in lung cancer, suggesting that ASF1B may provide a promising target for the therapy of lung cancer.

Reversine suppresses osteosarcoma cell growth through targeting BMP-Smad1/5/8-mediated angiogenesis.

Reversine, or 2-(4-morpholinoanilino)-6cyclohexylaminopurine, is a 2,6-disubstituted purine derivative. This small molecule exhibits tumor-suppressive activities through different molecular mechanisms. In this study, in vitro and in vivo angiogenic models were used to elucidate the effect of Reversine on angiogenesis in the tumor suppression. Firstly, we grafted osteosarcoma-derived MNNG/HOS cell aggregates onto chick embryonic chorioallantoic membrane (CAM) to examine the vascularization of these grafts following Reversine treatment. Following culture, it was determined that Reversine inhibited MNNG/HOS grafts growth, and decreased the density of blood vessels in the chick CAM. We then used CAM and chick embryonic yolk-sac membrane (YSM) to investigate the effects of Reversine on angiogenesis. The results revealed Reversine inhibited the proliferation of endothelial cells, where cells were mainly arrested at G1/S phase of the cell cycle. Scratch-wound assay with HUVECs revealed that Reversine suppressed cell migration in vitro. Furthermore, endothelial cells tube formation assay and chick aortic arch sprouting assay demonstrated Reversine inhibited the sprouting, migration of endothelial cells. Lastly, qPCR and western blot analyses showed BMP-associated Smad1/5/8 signaling expressions were up-regulated by Reversine treatment. Our results showed that Reversine could suppress tumor growth by inhibiting angiogenesis through BMP signaling, and suggests a potential use of Reversine as an anti-tumor therapy.

NEMA NU2-2012 performance measurements of the United Imaging uPMR790: an integrated PET/MR system.

PURPOSE: In this paper, we aimed to evaluate the positron emission tomography (PET) performance of, to the best of our knowledge, the third commercially available whole-body integrated PET/magnetic resonance (MR) system. METHODS: The PET system performance was measured following the NEMA standards with and without simultaneous MR operation. PET spatial resolution, sensitivity, scatter fraction, count-rate performance, accuracy of count losses and random corrections, image quality, and time-of-flight (TOF) resolution were quantitatively evaluated. Clinical scans were acquired at the PET/MR system and compared with images acquired at a PET/CT with the same digital detector technology. RESULTS: Measurement results of essential PET performance were reported in the form of MR idle (MR pulsing). The axial, radial, and tangential spatial resolutions were measured as 2.72 mm (2.73 mm), 2.86 mm (2.85 mm), and 2.81 mm (2.82 mm) FWHM, respectively, at 1 cm radial offset. The NECR peak was measured as 129.2 kcps (129.5 kcps) at 14.7 kBq mL-1 (14.2 kBq mL-1). The scatter fraction at NECR peak was 37.9% (36.5%), and the maximum slice error below NECR was 4.1% (4.5%). Contrast recovery coefficients ranged from 51.8% (52.3%) for 10 mm hot sphere to 87.3% (87.2%) for 37 mm cold sphere. TOF resolution at 5.3 kBq mL-1 was measured at 535 ps (540 ps). With point source, TOF was measured to be 474 ps (485 ps). Clinical scans revealed similar image quality from the PET/MR and the comparative PET/CT system. CONCLUSION: The PET performance of the newly introduced integrated PET/MR system is not significantly affected by the simultaneous operation of an MR sequence (2-point DIXON sequence). Measurement results demonstrate comparable performance with other state-of-the-art PET/MR systems. The clinical benefits of high spatial resolution and long axial coverage remain to be further evaluated in specific clinical imaging applications.

[Timing calibration comparison research of integrated TOF-PET/MR].

Integrated TOF-PET/MR is a multimodal imaging system which can acquire high-quality magnetic resonance (MR) and positron emission tomography (PET) images at the same time, and it has time of flight (TOF) function. The TOF-PET system usually features better image quality compared to traditional PET because it is capable of localizing the lesion on the line of response where annihilation takes place. TOF technology measures the time difference between the detectors on which the two 180-degrees-seperated photons generated from positron annihilation are received. Since every individual crystal might be prone to its timing bias, timing calibration is needed for a TOF-PET system to work properly. Three approaches of timing calibration are introduced in this article. The first one named as fan-beam method is an iterative method that measures the bias of the Gaussian distribution of timing offset created from a fan-beam area constructed using geometric techniques. The second one is to find solutions of the overdetermination equations set using L1 norm minimization and is called L1-norm method. The last one called L2-norm method is to build histogram of the TOF and find the peak, and uses L2 norm minimization to get the result. This article focuses on the comparison of the amount of the data and the calculation time needed by each of the three methods. To avoid location error of the cylinder radioactive source during data collection, we developed a location calibration algorithm which could calculate accurate position of the source and reduce image artifacts. The experiment results indicate that the three approaches introduced in this article could enhance the qualities of PET images and standardized uptake values of cancer regions, so the timing calibration of integrated TOF-PET/MR system was realized. The fan-beam method has the best image quality, especially in small lesions. In integrated TOF-PET/MR timing calibration, we recommend using fan-beam method.

Antithrombin nanoparticles improve kidney reperfusion and protect kidney function after ischemia-reperfusion injury.

In the extension phase of acute kidney injury, microvascular thrombosis, inflammation, vasoconstriction, and vascular endothelial cell dysfunction promote progressive damage to renal parenchyma after reperfusion. In this study, we hypothesized that direct targeting and pharmaceutical knockdown of activated thrombin at the sites of injury with a selective nanoparticle (NP)-based thrombin inhibitor, PPACK (phenylalanine-proline-arginine-chloromethylketone), would improve kidney reperfusion and protect renal function after transient warm ischemia in rodent models. Saline- or plain NP-treated animals were employed as controls. In vivo 19F magnetic resonance imaging revealed that kidney nonreperfusion was evident within 3 h after global kidney reperfusion at 34 ± 13% area in the saline group and 43 ± 12% area in the plain NP group and substantially reduced to 17 ± 4% (∼50% decrease, P < 0.05) in the PPACK NP pretreatment group. PPACK NP pretreatment prevented an increase in serum creatinine concentration within 24 h after ischemia-reperfusion, reflecting preserved renal function. Histologic analysis illustrated substantially reduced intrarenal thrombin accumulation within 24 h after reperfusion for PPACK NP-treated kidneys (0.11% ± 0.06%) compared with saline-treated kidneys (0.58 ± 0.37%). These results suggest a direct role for thrombin in the pathophysiology of AKI and a nanomedicine-based preventative strategy for improving kidney reperfusion after transient warm ischemia.

Overexpression of a miR393-resistant form of transport inhibitor response protein 1 (mTIR1) enhances salt tolerance by increased osmoregulation and Na+ exclusion in Arabidopsis thaliana.

Soil salinity is a common environmental stress factor that limits agricultural production worldwide. Plants have evolved different strategies to achieve salt tolerance. miR393 has been identified as closely related to biotic and abiotic stresses, and targets F-box genes that encode auxin receptors. The miR393-TIR1/AFB2/AFB3 regulatory module was discovered to have multiple functions that manipulate the auxin response. This study focused on miR393 and one of its targets, TIR1, and found that they played potential roles in response to salt stress. Our results showed that overexpression of a miR393-resistant TIR1 gene (mTIR1) in Arabidopsis clearly enhanced salt stress tolerance, which led to a higher germination rate, less water loss, reduced inhibition of root elongation, delayed senescence, decreased death rate and stabilized Chl content. These plants accumulated more proline and anthocyanin, and displayed enhanced osmotic stress tolerance. The expression of some salt stress-related genes was altered, and sodium content can be reduced in these plants under salt stress. We proposed that highly increased auxin signaling by overexpression of mTIR1 may trigger auxin-mediated downstream pathways to enhance plant salt stress resistance by osmoregulation and increased Na(+) exclusion.

Magnetic resonance imaging of melanoma exosomes in lymph nodes.

PURPOSE: Exosomes are cell derived extracellular nanovesicles that relay molecular signals pertinent to both normal physiologic and disease processes. The ability to modify and track exosomes in vivo is essential to understanding exosome pathogenesis, and for utilizing exosomes as effective diagnostic and therapeutic nanocarriers to treat diseases. METHODS: We recently reported a new electroporation method that allow exosomes to be loaded with superparamagnetic iron oxide nanoparticles for magnetic resonance tracking. RESULTS: Building on this approach, we now demonstrate for the first time using a C57BL/6 mouse model that melanoma exosomes can be imaged in vitro, and within lymph nodes in vivo with the use of standard MRI approaches. CONCLUSION: These findings demonstrate proof of principle that exosome biology can be followed in vivo and pave the way for the development of future diagnostic and therapeutic applications. Magn Reson Med 74:266-271, 2015. © 2014 Wiley Periodicals, Inc.

Assessing intrarenal nonperfusion and vascular leakage in acute kidney injury with multinuclear (1) H/(19) F MRI and perfluorocarbon nanoparticles.

PURPOSE: We sought to develop a unique sensor-reporter approach for functional kidney imaging that employs circulating perfluorocarbon nanoparticles and multinuclear (1) H/(19) F MRI. METHODS: (19) F spin density weighted and T1 weighted images were used to generate quantitative functional mappings of both healthy and ischemia-reperfusion (acute kidney injury) injured mouse kidneys. (1) H blood-oxygenation-level-dependent (BOLD) MRI was also employed as a supplementary approach to facilitate the comprehensive analysis of renal circulation and its pathological changes in acute kidney injury. RESULTS: Heterogeneous blood volume distributions and intrarenal oxygenation gradients were confirmed in healthy kidneys by (19) F MRI. In a mouse model of acute kidney injury, (19) F MRI, in conjunction with blood-oxygenation-level-dependent MRI, sensitively delineated renal vascular damage and recovery. In the cortico-medullary junction region, we observed 25% lower (19) F signal (P < 0.05) and 70% longer (1) H T2* (P < 0.01) in injured kidneys compared with contralateral kidneys at 24 h after initial ischemia-reperfusion injury. We also detected 71% higher (19) F signal (P < 0.01) and 40% lower (1) H T2* (P < 0.05) in the renal medulla region of injured kidneys compared with contralateral uninjured kidneys. CONCLUSION: Integrated (1) H/(19) F MRI using perfluorocarbon nanoparticles provides a multiparametric readout of regional perfusion defects in acutely injured kidneys.

Programmable nanoparticle functionalization for in vivo targeting.

The emerging demand for programmable functionalization of existing base nanocarriers necessitates development of an efficient approach for cargo loading that avoids nanoparticle redesign for each individual application. Herein, we demonstrate in vivo a postformulation strategy for lipidic nanocarrier functionalization with the use of a linker peptide, which rapidly and stably integrates cargos into lipidic membranes of nanocarriers after simple mixing through a self-assembling process. We exemplified this strategy by generating a VCAM-1-targeted perfluorocarbon nanoparticle for in vivo targeting in atherosclerosis (ApoE-deficient) and breast cancer (STAT-1-deficient) models. In the atherosclerotic model, a 4.1-fold augmentation in binding to affected aortas was observed for targeted vs. nontargeted nanoparticles (P<0.0298). Likewise, in the breast cancer model, a 4.9-fold increase in the nanoparticle signal from tumor vasculature was observed for targeted vs. nontargeted nanoparticles (P<0.0216). In each case, the nanoparticle was registered with fluorine ((19)F) magnetic resonance spectroscopy of the nanoparticle perfluorocarbon core, yielding a quantitative estimate of the number of tissue-bound nanoparticles. Because other common nanocarriers with lipid coatings (e.g., liposomes, micelles, etc.) can employ this strategy, this peptide linker postformulation approach is applicable to more than half of the available nanosystems currently in clinical trials or clinical uses.

Regional changes in brain metabolism during the progression of mild cognitive impairment: a longitudinal study based on radiomics.

BACKGROUND: This study aimed to establish radiomics models based on positron emission tomography (PET) images to longitudinally predict transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: In our study, 278 MCI patients from the ADNI database were analyzed, where 60 transitioned to AD (pMCI) and 218 remained stable (sMCI) over 48 months. Patients were divided into a training set (n = 222) and a validation set (n = 56). We first employed voxel-based analysis of 18F-FDG PET images to identify brain regions that present significant SUV difference between pMCI and sMCI groups. Radiomic features were extracted from these regions, key features were selected, and predictive models were developed for individual and combined brain regions. The models' effectiveness was evaluated using metrics like AUC to determine the most accurate predictive model for MCI progression. RESULTS: Voxel-based analysis revealed four brain regions implicated in the progression from MCI to AD. These include ROI1 within the Temporal lobe, ROI2 and ROI3 in the Thalamus, and ROI4 in the Limbic system. Among the predictive models developed for these individual regions, the model utilizing ROI4 demonstrated superior predictive accuracy. In the training set, the AUC for the ROI4 model was 0.803 (95% CI 0.736, 0.865), and in the validation set, it achieved an AUC of 0.733 (95% CI 0.559, 0.893). Conversely, the model based on ROI3 showed the lowest performance, with an AUC of 0.75 (95% CI 0.685, 0.809). Notably, the comprehensive model encompassing all identified regions (ROI total) outperformed the single-region models, achieving an AUC of 0.884 (95% CI 0.845, 0.921) in the training set and 0.816 (95% CI 0.705, 0.909) in the validation set, indicating significantly enhanced predictive capability for MCI progression to AD. CONCLUSION: Our findings underscore the Limbic system as the brain region most closely associated with the progression from MCI to AD. Importantly, our study demonstrates that a PET brain radiomics model encompassing multiple brain regions (ROI total) significantly outperforms models based on single brain regions. This comprehensive approach more accurately identifies MCI patients at high risk of progressing to AD, offering valuable insights for non-invasive diagnostics and facilitating early and timely interventions in clinical settings.

A prognostic model for triple-negative breast cancer patients with liver metastasis: A population-based study.

However, it is still difficult for clinicians to establish prognostic stratifications and therapeutic strategies because of the lack of tools for predicting the survival of triple-negative breast cancer patients with liver metastases (TNBC-LM). Based on clinical data from large populations, a sensitive and discriminative nomogram was developed and validated to predict the prognosis of TNBC patients with LM at initial diagnosis or at the later course. Introduction/background: Liver metastasis (LM) in TNBC patients is associated with significant morbidity and mortality. The objective of this study was to construct a clinical model to predict the survival of TNBC-LM patients. Materials and methods: Clinicopathologic data were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and the Fifth Affiliated Hospital of Sun Yat-Sen University (FAFSYU). Based on patients with newly diagnosed TNBC with LM (nTNBC-LM) from the SEER database, a predictive nomogram was established and validated. Its predictive effect on TNBC patients with LM at later disease course by enrolling TNBC patients from FAFSYU who developed LM later. The prognostic effect of different treatment for nTNBC-LM was further assessed. Results: A prognostic model was developed and validated to predict the prognosis of TNBC-LM patients. For LM patients diagnosed at the initial or later treatment stage, the C-index (0.712, 0.803 and 0.699 in the training, validation and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the nomogram. Surgical resection on the primary tumour and chemotherapy were found to be associated with significantly better overall survival (OS). Conclusion: A sensitive and discriminative model was developed to predict OS in TNBC-LM patients both at and after initial diagnosis.

Performance Characteristics of the NeuroEXPLORER, a Next-Generation Human Brain PET/CT Imager.

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.5 cm) to enhance sensitivity. Here, we present the physical characterization, performance evaluation, and first human images of the NeuroEXPLORER. Methods: Measurements of spatial resolution, sensitivity, count rate performance, energy and timing resolution, and image quality were performed adhering to the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. The system's performance was demonstrated through imaging studies of the Hoffman 3-dimensional brain phantom and the mini-Derenzo phantom. Initial 18F-FDG images from a healthy volunteer are presented. Results: With filtered backprojection reconstruction, the radial and tangential spatial resolutions (full width at half maximum) averaged 1.64, 2.06, and 2.51 mm, with axial resolutions of 2.73, 2.89, and 2.93 mm for radial offsets of 1, 10, and 20 cm, respectively. The average time-of-flight resolution was 236 ps, and the energy resolution was 10.5%. NEMA sensitivities were 46.0 and 47.6 kcps/MBq at the center and 10-cm offset, respectively. A sensitivity of 11.8% was achieved at the FOV center. The peak noise-equivalent count rate was 1.31 Mcps at 58.0 kBq/mL, and the scatter fraction at 5.3 kBq/mL was 36.5%. The maximum count rate error at the peak noise-equivalent count rate was less than 5%. At 3 iterations, the NEMA image-quality contrast recovery coefficients varied from 74.5% (10-mm sphere) to 92.6% (37-mm sphere), and background variability ranged from 3.1% to 1.4% at a contrast of 4.0:1. An example human brain 18F-FDG image exhibited very high resolution, capturing intricate details in the cortex and subcortical structures. Conclusion: The NeuroEXPLORER offers high sensitivity and high spatial resolution. With its long axial length, it also enables high-quality spinal cord imaging and image-derived input functions from the carotid arteries. These performance enhancements will substantially broaden the range of human brain PET paradigms, protocols, and thereby clinical research applications.

Cardiomyocyte architectural plasticity in fetal, neonatal, and adult pig hearts delineated with diffusion tensor MRI.

Cardiomyocyte organization is a critical determinant of coordinated cardiac contractile function. Because of the acute opening of the pulmonary circulation, the relative workload of the left ventricle (LV) and right ventricle (RV) changes substantially immediately after birth. We hypothesized that three-dimensional cardiomyocyte architecture might be required to adapt rapidly to accommodate programmed perinatal changes of cardiac function. Isolated fixed hearts from pig fetuses or pigs at midgestation, preborn, postnatal day 1 (P1), postnatal day 5, postnatal day 14 (P14), and adulthood (n = 5 for each group) were acquired for diffusion-weighted magnetic resonance imaging. Cardiomyocyte architecture was visualized by three-dimensional fiber tracking and was quantitatively evaluated by the measured helix angle (α(h)). Upon the completion of MRI, hearts were sectioned and stained with hematoxylin/eosin (H&E) to evaluate cardiomyocyte alignment, with picrosirius red to evaluate collagen content, and with anti-Ki67 to evaluate postnatal cell proliferation. The helical architecture of cardiomyocyte was observed as early as the midgestational period. Postnatal changes of cardiomyocyte architecture were observed from P1 to P14, which primary occurred in the septum and RV free wall (RVFW). In the septum, the volume ratio of LV- vs. RV-associated cardiomyocytes rapidly changed from RV-LV balanced pattern at birth to LV dominant pattern by P14. In the RVFW, subendocardial α(h) decreased by ~30° from P1 to P14. These findings indicate that the helical architecture of cardiomyocyte is developed as early as the midgestation period. Substantial and rapid adaptive changes in cardiac microarchitecture suggested considerable developmental plasticity of cardiomyocyte form and function in the postnatal period in response to altered cardiac mechanical function.

Rapid quantification of oxygen tension in blood flow with a fluorine nanoparticle reporter and a novel blood flow-enhanced-saturation-recovery sequence.

We present a novel blood flow-enhanced-saturation-recovery (BESR) sequence, which allows rapid in vivo T1 measurement of blood for both (1)H and (19)F nuclei. BESR sequence is achieved by combining homogeneous spin preparation and time-of-flight image acquisition and therefore preserves high time efficiency and signal-to-noise ratio for (19)F imaging of circulating perfluorocarbon nanoparticles comprising a perfluoro-15-crown-5-ether core and a lipid monolayer (nominal size = 250 nm). The consistency and accuracy of the BESR sequence for measuring T1 of blood was validated experimentally. With a confirmed linear response feature of (19)F R1 with oxygen tension in both salt solution and blood sample, we demonstrated the feasibility of the BESR sequence to quantitatively determine the oxygen tension within mouse left and right ventricles under both normoxia and hyperoxia conditions. Thus, (19)F BESR MRI of circulating perfluorocarbon nanoparticles represents a new approach to noninvasively evaluate intravascular oxygen tension.