Accelerated Cardiac Diffusion Tensor Imaging Using Joint Low-Rank and Sparsity Constraints

Objective: The purpose of this manuscript is to accelerate cardiac diffusion tensor imaging (CDTI) by integrating low-rankness and compressed sensing. Methods: Diffusion-weighted images exhibit both transform sparsity and low-rankness. These properties can jointly be exploited to accelerate CDTI, especially when a phase map is applied to correct for the phase inconsistency across diffusion directions, thereby enhancing low-rankness. The proposed method is evaluated both ex vivo and in vivo, and is compared to methods using either a low-rank or sparsity constraint alone. Results: Compared to using a low-rank or sparsity constraint alone, the proposed method preserves more accurate helix angle features, the transmural continuum across the myocardium wall, and mean diffusivity at higher acceleration, while yielding significantly lower bias and higher intraclass correlation coefficient. Conclusion: Low-rankness and compressed sensing together facilitate acceleration for both ex vivo and in vivo CDTI, improving reconstruction accuracy compared to employing either constraint alone. Significance: Compared to previous methods for accelerating CDTI, the proposed method has the potential to reach higher acceleration while preserving myofiber architecture features which may allow more spatial coverage, higher spatial resolution and shorter temporal footprint in the future.Comment: 11 pages, 16 figures, published on IEEE Transactions on Biomedical Engineerin

Pulmonary capillary hemangiomatosis: a lesson learned

Pulmonary capillary hemangiomatosis (PCH) is a rare and controversial entity that is known to be a cause of pulmonary hypertension and is microscopically characterized by proliferation of dilated capillary-sized channels along and in the alveolar walls. Clinically, it is mostly seen in adults. Clinical features are characterized by nonspecific findings such as shortness of breath, cough, chest pain, and fatigue. It can be clinically indistinguishable from pre-capillary pulmonary arterial hypertension disorders such as primary pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension. However, the diagnostic distinction, which usually requires a multidisciplinary approach, is crucial in order to avoid inappropriate treatment with vasodilator medications usually used for PAH treatment. Prognosis of PCH remains poor with lung transplant being the only definitive treatment. We report an autopsy case of pulmonary capillary hemangiomatosis unmasked at autopsy that was treated with a prostacyclin analog, usually contraindicated in such patients. We emphasize that this entity should always be on the differential diagnosis in a patient with pulmonary hypertension and requires great vigilance on the part of the clinician, radiologist and pathologist to make the diagnosis and guide appropriate management

Cellular Postconditioning: Allogeneic Cardiosphere-Derived Cells Reduce Infarct Size and Attenuate Microvascular Obstruction When Administered After Reperfusion in Pigs With Acute Myocardial Infarction

Intracoronary (IC) delivery of cardiosphere-derived cells (CDCs) has been demonstrated to be safe and effective in porcine and human chronic myocardial infarction (MI). However, IC delivery of CDCs after reperfusion in acute MI has never been assessed in a clinically-relevant large animal model. We tested CDCs as adjunctive therapy to reperfusion in a porcine model of MI

Multiplexed Quantum Dot Labeling of Activated c-Met Signaling in Castration-Resistant Human Prostate Cancer

The potential application of multiplexed quantum dot labeling (MQDL) for cancer detection and prognosis and monitoring therapeutic responses has attracted the interests of bioengineers, pathologists and cancer biologists. Many published studies claim that MQDL is effective for cancer biomarker detection and useful in cancer diagnosis and prognosis, these studies have not been standardized against quantitative biochemical and molecular determinations. In the present study, we used a molecularly characterized human prostate cancer cell model exhibiting activated c-Met signaling with epithelial to mesenchymal transition (EMT) and lethal metastatic progression to bone and soft tissues as the gold standard, and compared the c-Met cell signaling network in this model, in clinical human prostate cancer tissue specimens and in a castration-resistant human prostate cancer xenograft model. We observed c-Met signaling network activation, manifested by increased phosphorylated c-Met in all three. The downstream survival signaling network was mediated by NF-κB and Mcl-1 and EMT was driven by receptor activator of NF-κB ligand (RANKL), at the single cell level in clinical prostate cancer specimens and the xenograft model. Results were confirmed by real-time RT-PCR and western blots in a human prostate cancer cell model. MQDL is a powerful tool for assessing biomarker expression and it offers molecular insights into cancer progression at both the cell and tissue level with high degree of sensitivity

Allogeneic Cardiospheres Delivered via Percutaneous Transendocardial Injection Increase Viable Myocardium, Decrease Scar Size, and Attenuate Cardiac Dilatation in Porcine Ischemic Cardiomyopathy

BackgroundEpicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI), but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy.Methods and ResultsWe studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22) post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled (“dose optimization”) study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16). Finally, the superior product and dose (150 million cardiospheres) were tested in a blinded, randomized, placebo-controlled (“pivotal”) study (n = 22). Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells) was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo.ConclusionsDose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration

Reporting trends, practices, and resource utilization in neuroendocrine tumors of the prostate gland: a survey among thirty-nine genitourinary pathologists

Background: Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods: Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results: A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion: There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland

The Degradation Interface of Magnesium Based Alloys in Direct Contact with Human Primary Osteoblast Cells.

Magnesium alloys have been identified as a new generation material of orthopaedic implants. In vitro setups mimicking physiological conditions are promising for material / degradation analysis prior to in vivo studies however the direct influence of cell on the degradation mechanism has never been investigated. For the first time, the direct, active, influence of human primary osteoblasts on magnesium-based materials (pure magnesium, Mg-2Ag and Mg-10Gd alloys) is studied for up to 14 days. Several parameters such as composition of the degradation interface (directly beneath the cells) are analysed with a scanning electron microscope equipped with energy dispersive X-ray and focused ion beam. Furthermore, influence of the materials on cell metabolism is examined via different parameters like active mineralisation process. The results are highlighting the influences of the selected alloying element on the initial cells metabolic activity

Effect of seawater transfer on CYP1A gene expression in rainbow trout gills

International audienceDuring the transfer of rainbow trout from freshwater to seawater, the gills have to switch from an ion-absorption epithelium to an ion-secretion epithelium in order to maintain equilibrium of their hydromineral balance. After a change to ambient salinity, several gill modifications have already been demonstrated, including ion transporters. In order to identify new branchial mechanisms implicated in seawater acclimation, we carried out an extensive analysis of gene expression in gills using microarray technology. This strategy allowed us to show that CYP1A gene expression was up-regulated in the gills after salinity transfer. This increase was confirmed by real-time reverse transcription PCR. Furthermore, measurements of CYP1A enzyme activity (EROD) showed a significant increase after transfer to seawater. Immunohistochem-istry analysis in the gills revealed that cells with a higher expression of CYP1A protein were principally pillar cells and those in the primary lamellae not in contact with the external medium. The results of this study suggest for the first time that CYP1A may be implicated in the seawater acclimation of the gills of rainbow trout

Expression of CD56 and WT1 in ovarian stroma and ovarian stromal tumors

The immunophenotype of ovarian stroma and spindle cell tumors derived from ovarian stroma has not been well studied. We studied the expression of CD56, WT1, estrogen receptor-β (ER-& eta;), progesterone receptor (PR), smooth muscle actin, S-100, CD34, and muscle specific actin in 16 normal ovaries, 17 ovarian fibromas, 11 ovarian cellular fibromas, 10 ovarian fibrothecomas, and 11 ovarian leiomyomas. In addition, we studied CD56 and WT1 expression in 7 cases of normal endometrium, 8 uterine smooth muscle tumors, 5 endometrial stromal tumors and 64 nongynecologic (GYN) spindle cell sarcomas. All normal ovaries, ovarian fibromas, fibrothecomas, and ovarian leiomyomas were positive for CD56 and WT1. Most of the normal ovaries, ovarian fibromas, ovarian fibrothecomas, and ovarian leiomyomata also expressed ER-β and PR. Eight of 17 ovarian fibromas, 5 of 11 ovarian cellular fibromas, and 4 of 10 ovarian fibrothecoma with focal fibroblastic differentiation were positive for smooth muscle actin. A few cases of these tumors also expressed S-100 and CD34. Only rare cases of non-GYN spindle cell sarcomas expressed WT1. Our study results show that ovarian fibromas, fibrothecomas, and leiomyomas have a similar immunophenotype (positive for CD56, WT1, ER-β, and PR) to that of ovarian stromal cells, supporting an ovarian stromal origin for these neoplasms. However, unlike normal ovarian stromal cells, ovarian fibromas, fibrothecomas, and leiomyomas can also show fibroblastic, smooth muscle, Schwannian, and solitary fibrous tumorlike differentiation. WT1 is a fairly specific marker for spindle cell tumors of gynecologic organs, including ovarian spindle cell tumors, endometrial stromal tumors, and uterine smooth muscle tumors. Non-GYN spindle cell sarcomas rarely express WT1. CD56 is strongly expressed in ovarian stromal cells but not in endometrial stromal cells. CD56 is often expressed by a wide variety of spindle cell sarcomas, thus, it has no value in differentiating GYN from non-GYN spindle cell tumors. © 2008 by Lippincott Williams & Wilkins