Areas Of Normal Tissue Research Articles

Accessory sple­en in a dog: Macroscopic and microscopic findings

Accessory spleens are one or more areas of normal ectopic splenic tissue of variable size supplied by the branches of the splenic artery. A 7 year-old mixed breed male dog was fixed for use as a model in anatomy hall. During the abdominal dissection, the gross examination showed a 6.3×3.1×1 cm mass that was situated on the caudodorsal border of the spleen. Its appearance and firm consistency were similar to those of spleen. There was no connection between the spleen and this mass. It was supplied by accessory splenic artery. Microscopic examination of the mass revealed some structures similar to spleen.

Pathological Analysis of Lung Metastasis Following Lateral Tail-Vein Injection of Tumor Cells.

Metastasis, the primary cause of morbidity and mortality for most cancer patients, can be challenging to model preclinically in mice. Few spontaneous metastasis models are available. Thus, the experimental metastasis model involving tail-vein injection of suitable cell lines is a mainstay of metastasis research. When cancer cells are injected into the lateral tail-vein, the lung is their preferred site of colonization. A potential limitation of this technique is the accurate quantification of the metastatic lung tumor burden. While some investigators count macrometastases of a pre-defined size and/or include micrometastases following sectioning of tissue, others determine the area of metastatic lesions relative to normal tissue area. Both of these quantification methods can be exceedingly difficult when the metastatic burden is high. Herein, we demonstrate an intravenous injection model of lung metastasis followed by an advanced method for quantifying metastatic tumor burden using image analysis software. This process allows for investigation of multiple end-point parameters, including average metastasis size, total number of metastases, and total metastasis area, to provide a comprehensive analysis. Furthermore, this method has been reviewed by a veterinary pathologist board-certified by the American College of Veterinary Pathologists (SEK) to ensure accuracy.

Intratumoral Heterogeneity of Expression of 16 miRNA in Luminal Cancer of the Mammary Gland.

The purpose of this work is to determine the intratumoral distribution of miRNA expression profiles in luminal breast cancer (BC). The study included 33 certain BC cases of the luminal A or luminal B (Her2-) subtypes. The relative expression levels of miRNA-20a; -21; -125b; -126; -200b; -181a; -205; -221; -222; -451a; -99a; -145; -200a; -214; -30a; -191; and small nuclear RNAs U6, U54, and U58 were measured by RT-qPCR in four intratumor areas in each of 33 luminal BC specimens and in surrounding normal mammary gland tissues. Comparative analysis of miRNA expression levels between normal mammary gland tissue and different intratumor areas revealed that only four miRNAs (miRNA-21, -200b, -200a, -191) appear as consistently differentiating markers. A comparative analysis of miRNA expression levels between normal mammary gland tissue and the tumor border revealed statistically significant differences for ten miRNAs; 10 miRNAs show differential expression between normal mammary gland tissue and central tumor specimens; 9 miRNAs show differential expression between normal mammary gland tissue and tumor periphery 1; 13 miRNAs show differential expression between normal mammary gland tissue and tumor periphery 2. After comparing the tumor periphery 1 and tumor center, we found statistically significant differences in expression between five miRNAs and after comparing the tumor periphery 2 and tumor center, differences were observed for 12 miRNAs. MiRNA expression levels are subject to considerable variation, depending on the intratumor area. This may explain the inconsistency in miRNA expression estimates in BC coming from different laboratories.

Discovery of novel biomarkers for atherosclerotic aortic aneurysm through proteomics-based assessment of disease progression

Since aortic aneurysms (AAs) are mostly asymptomatic, but they have a high mortality rate upon rupture, their detection and progression evaluation are clinically important issues. To discover diagnostic biomarkers for AA, we performed proteome analysis of aortic media from patients with thoracic atherosclerotic AA (TAAA), comparing protein levels between the aneurysm and normal tissue areas. After hierarchical clustering analysis of the proteome analysis data, tissue samples were classified into three groups, regardless of morphological features. This classification was shown to reflect disease progression stage identified by pathological examination. This proteomics-based staging system enabled us to identify more significantly altered proteins than the morphological classification system. In subsequent data analysis, Niemann-Pick disease type C2 protein (NPC2) and insulin-like growth factor-binding protein 7 (IGFBP7) were selected as novel biomarker candidates for AA and were compared with the previously reported biomarker, thrombospondin 1 (THBS1). Blood concentrations of NPC2 and IGFBP7 were significantly increased, while THBS1 levels were decreased in TAAA and abdominal atherosclerotic AA patients. Receiver operating characteristic analysis of AA patients and healthy controls showed that NPC2 and IGFBP7 have higher specificity and sensitivity than THBS1. Thus, NPC2 and IGFBP7 are promising biomarkers for the detection and progression evaluation of AA.

Pharmacological correction of periodontitis using synthetic analogues of indolicidin

Introduction: The leading role of pathogenic microorganisms in the pathogenesis of periodontitis is beyond doubt. However, the use of antibiotics for periodontitis is associated with a number of problems. Indolicidins have a unique anti-microbial effect. The relevance of the search for new drugs for the treatment of acute periodontitis based on the natural indolicidin peptide becomes obvious.
 Materials and methods: The investigation was performed on 320 Wistar male rats, using synthetic analogues of natural indolicidin: No. 7 and No. 8, which were administered intraperitoneally at a dose of 500 µg/kg in a volume of 0.2 ml once a day for 7 days. Periodontitis was simulated in animals according to the method proposed by Volozhin A.I. and Vinogradova S.I.
 Results and discussion: The correcting effect of indolicidin analogues on the periodontitis course, was manifested by a decrease in edema and in the relative area of cell infiltrates, a significant increase in the relative area of normal tissue, and a correction of the periodontal composition. The use of indolicidin analogues led to an increase in the functional activity of neutrophils and macrophages, acute phase proteins concentration, a correction of pro-oxidantantioxidant balance and production of vasoactive substances. The effect of indolicidin analogues was higher than that of lincomycin. The greater effectiveness of peptide No.8 compared to that of No.7 was established.
 Conclusion: The investigation opens up the prospects of the synthesis of new antimicrobial drugs on the basis of the synthetic analogues of indolicidin.

Learning to detect lymphocytes in immunohistochemistry with deep learning.

The immune system is of critical importance in the development of cancer. The evasion of destruction by the immune system is one of the emerging hallmarks of cancer. We have built a dataset of 171,166 manually annotated CD3+ and CD8+ cells, which we used to train deep learning algorithms for automatic detection of lymphocytes in histopathology images to better quantify immune response. Moreover, we investigate the effectiveness of four deep learning based methods when different subcompartments of the whole-slide image are considered: normal tissue areas, areas with immune cell clusters, and areas containing artifacts. We have compared the proposed methods in breast, colon and prostate cancer tissue slides collected from nine different medical centers. Finally, we report the results of an observer study on lymphocyte quantification, which involved four pathologists from different medical centers, and compare their performance with the automatic detection. The results give insights on the applicability of the proposed methods for clinical use. U-Net obtained the highest performance with an F1-score of 0.78 and the highest agreement with manual evaluation (κ=0.72), whereas the average pathologists agreement with reference standard was κ=0.64. The test set and the automatic evaluation procedure are publicly available at lyon19.grand-challenge.org.

Macroscopic and microscopic fluorescence spectroscopy of colorectal benign and malignant lesions - diagnostically important features.

Fluorescence spectroscopy is a sensitive, fast and non-invasive tool for a diagnostics of cancerous gastrointestinal lesions. It could be applied for in situ detection of tumours during primary endoscopic observations or as add-on measurement modality during microscopic observations of tissue histology slides for their initial or retrospective diagnosis. Therefore, we are looking for diagnostically important features of normal and cancerous tissue areas in a broad spectral range for gastrointestinal tissues ex vivo using two steady-state macroscopic fluorescent spectroscopic modalities and by confocal fluorescent microscopic detection. Results obtained from autofluorescence spectroscopy of benign and malignant lower part gastrointestinal tract (GIT) lesions from freshly excised tissues during surgical removal of the lesions in 18 patients (22 lesions), were compared with the spectral measurements obtained during confocal fluorescent microscopy observations of unstained tissue slides using 405 nm excitation. Excitation-emission matrices (EEMs) were used for ex vivo measurements with applied excitation in 280-440 nm spectral region and emission observed between 300 and 700 nm. Synchronous fluorescence spectroscopy (SFS) approach was also applied to improve the spectral resolution of the observed complex emission spectra. Specific fluorescent features observed, related to presence of structural proteins, co-enzymes and endogenous porphyrins in the tissues investigated, allow discriminating normal mucosa from benign polyps and malignant carcinoma lesions with diagnostic accuracy up to 94.4%.

Correction of Acute Parodontitis with Indolicidin Analogues.

We studied the influence of synthetic indolicidin analogues on the development of acute periodontitis. The corrective effect was found in indolicidin analogues Nos. 7 and 8; it manifested in a decrease in the edema of gingival epithelium and lamina propria, a decrease in the relative area of inflammatory infiltrates, and a significant increase in the relative area of normal connective tissue. These changes were revealed as soon as on day 14 and were most pronounced in 21 days after the removal of the ligature. Indolicidin analogues Nos. 7 and 8 demonstrated similar effectiveness on the model of acute periodontitis.

Background parenchymal enhancement on breast MRI: A comprehensive review.

The degree of normal fibroglandular tissue that enhances on breast MRI, known as background parenchymal enhancement (BPE), was initially described as an incidental finding that could affect interpretation performance. While BPE is now established to be a physiologic phenomenon that is affected by both endogenous and exogenous hormone levels, evidence supporting the notion that BPE frequently masks breast cancers is limited. However, compelling data have emerged to suggest BPE is an independent marker of breast cancer risk and breast cancer treatment outcomes. Specifically, multiple studies have shown that elevated BPE levels, measured qualitatively or quantitatively, are associated with a greater risk of developing breast cancer. Evidence also suggests that BPE could be a predictor of neoadjuvant breast cancer treatment response and overall breast cancer treatment outcomes. These discoveries come at a time when breast cancer screening and treatment have moved toward an increased emphasis on targeted and individualized approaches, of which the identification of imaging features that can predict cancer diagnosis and treatment response is an increasingly recognized component. Historically, researchers have primarily studied quantitative tumor imaging features in pursuit of clinically useful biomarkers. However, the need to segment less well-defined areas of normal tissue for quantitative BPE measurements presents its own unique challenges. Furthermore, there is no consensus on the optimal timing on dynamic contrast-enhanced MRI for BPE quantitation. This article comprehensively reviews BPE with a particular focus on its potential to increase precision approaches to breast cancer risk assessment, diagnosis, and treatment. It also describes areas of needed future research, such as the applicability of BPE to women at average risk, the biological underpinnings of BPE, and the standardization of BPE characterization. Level of Evidence: 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:43-61.

Two-photon fluorescence imaging of lipid drops polarity toward cancer diagnosis in living cells and tissue

Monitoring the polarity of intracellular lipid droplets (LDs) is of great importance toward cancer diagnosis. Herein, we have rationally designed a novel LDs-targeting and polarity-sensitive fluorescent probe CBMC, which contains carbazole as an electron-donating group and malononitrile as an electron-accepting group forming intramolecular charge transfer mechanism. Due to its excellent solvatochromism, the probe emits stronger fluorescence in normal cells but weaker in cancer cells. By means of CBMC, normal tissues with stronger fluorescence have been obviously pointed out from cancerous tissues. For cancer therapy, the probe CBMC could be an ideal candidate to evaluate tumor, because the tumor area would decrease while the normal tissue area would increase with treatment time. Compared with existing probes with turn-off signal to normal cells, such a new probe with turn on type in normal cells could provide more reliable information with advantages of lower background interference, higher signal to noise ratio, and higher sensitivity. This probe CBMC will be a powerful tool to be potentially applied in tumor diagnosis in the case of treatment.

Disrupted circadian clocks and altered tissue mechanics in primary human breast tumours

BackgroundCircadian rhythms maintain tissue homeostasis during the 24-h day-night cycle. Cell-autonomous circadian clocks play fundamental roles in cell division, DNA damage responses and metabolism. Circadian disruptions have been proposed as a contributing factor for cancer initiation and progression, although definitive evidence for altered molecular circadian clocks in cancer is still lacking. In this study, we looked at circadian clocks in breast cancer.MethodsWe isolated primary tumours and normal tissues from the same individuals who had developed breast cancer with no metastases. We assessed circadian clocks within primary cells of the patients by lentiviral expression of circadian reporters, and the levels of clock genes in tissues by qPCR. We histologically examined collagen organisation within the normal and tumour tissue areas, and probed the stiffness of the stroma adjacent to normal and tumour epithelium using atomic force microscopy.ResultsEpithelial ducts were disorganised within the tumour areas. Circadian clocks were altered in cultured tumour cells. Tumour regions were surrounded by stroma with an altered collagen organisation and increased stiffness. Levels of Bmal1 messenger RNA (mRNA) were significantly altered in the tumours in comparison to normal epithelia.ConclusionCircadian rhythms are suppressed in breast tumour epithelia in comparison to the normal epithelia in paired patient samples. This correlates with increased tissue stiffness around the tumour region. We suggest possible involvement of altered circadian clocks in the development and progression of breast cancer.

Molecular progression to cervical precancer, epigenetic switch or sequential model?

The evolution of precancerous cervical lesions is poorly understood. A widely held model of cervical intraepithelial neoplasia grade 3 (CIN3) development is sequential progression from normal through CIN1 and CIN2 to CIN3. Another hypothesis, the “molecular switch” model, postulates that CIN3 can evolve directly from human papillomavirus (HPV)‐infected normal epithelium without progressing through CIN1 and CIN2. To shed light on this process, we compared DNA methylation of selected human biomarkers and HPV types in two groups of CIN1: CIN1 that were near or adjacent to CIN3 (adjacent‐CIN1) and CIN1 that were the principal lesions with no CIN3 detected (principal‐CIN1). 354 CIN (CIN1 and CIN3) and normal tissue areas were dissected and typed for HPV from 127 women who underwent loop electrosurgical excision procedures (LEEP). Methylation of genes EPB41L3 and the viral regions of HPV16‐L1/L2, HPV18‐L2, HPV31‐L1, and HPV33‐L2 were determined by a highly accurate quantitative pyrosequencing of bisulfite converted DNA. There was a significant trend of increased methylation with disease grade comparing normal to CIN1 and CIN3 (p < 0.0001). Adjacent‐CIN1 predominantly shared the same HPV types as the CIN3, however, methylation differed substantially between adjacent‐CIN1 and CIN3 (p = 0.008). In contrast diagnostically principal‐CIN1 had an indistinguishable methylation distribution compared to adjacent‐CIN1 (EPB41L3: p = 0.49; HPVme‐All: p = 0.11). Our results suggest that progression from normal epithelium to CIN1 or CIN3 is usually promoted by the same HPV type but occurs via distinct DNA epigenotypes, thus favoring the “molecular switch” model.

Abstract 5057: Exposure to highly energetic charged (hze) particle radiation is associated with higher colitis and colorectal cancer incidence in IL10-/- mice

Abstract Epidemiological data from atom-bomb survivors and from radiotherapy patients have highlight an underlying risk of colitis and colorectal cancer (CRC) after ionizing radiation-exposure. In contrast, astronauts planning to undertake deep space exploration such as mission to Mars have risk of radiation exposure from highly energetic charged (HZE) particles present in galactic cosmic radiation (GCR) and risk of colitis and CRC after HZE-exposure is yet to be determined. Therefore, animal studies are warranted to address existing uncertainties in colitis and CRC risk prediction after exposure to HZE radiation. Here we report IL10-/- mice as a suitable mouse model for assessment of colitis and CRC risk after exposure to space radiation. Male mice (n=12 mice/group) were whole-body exposed to sham-radiation, γ-rays and 28Si-ion (300 MeV/n; 70 keV/μm; 1.4 Gy). Mice were sacrificed three months after irradiation, and colon swiss-rolls sections were analyzed for colitis and CRC grade was noted in hematoxylin and eosin stained sections. Immunohistochemistry (β-catenin, Cyclin-D1, phospho-H3, iNOS, phoshoNfKβ-p65, and Cox2) was also performed to assess HZE-induced proliferative and inflammatory signaling. Further, inflammation-associated gene-expression analysis was also conducted in both radiation-induced tumor and adjoining normal tissue area. Here we report that relative to controls and γ-ray, colitis score, colon tumor incidence, size and grade was significantly higher after space (28Si-ion) radiation exposure. Higher number of phospho-H3 positive cells in 28Si-ion exposed mouse colon demonstrated increased proliferative index and in increased colon tumors of higher grade, could be due to greater activation of β-catenin and its downstream effector cyclin D1. In addition, higher accumulation of iNOS, phoshoNfKβ-p65, and Cox2 in stromal and epithelial cells after space radiation exposure clearly indicates upregulation of both immune and epithelial inflammation as drivers of colitis and CRC development. Inflammation associated protein markers and gene expression signatures were more pronounced after 28Si-ion exposure. Significant up-regulation of GATA4, ICAM1, ITGA2 and EGFR were exclusive to 28Si-ion exposed mouse colon, however PTGES and TGFβ1 were upregulated in both γ and 28Si-ion exposed mice. Overall, this study suggests that IL10-/- mouse are a suitable model to assess IR-induced colitis and CRC risk, and that space radiation carries higher risk of colitis and CRC incidence, relative to γ-rays at comparable doses. This study has implications for risk prediction in astronauts planning for deep space mission and also for cancer patients planning to undergo particle radiotherapy. Citation Format: Shubhankar Suman, Bo-Hyun Moon, Albert J. Fornace, Kamal Datta. Exposure to highly energetic charged (hze) particle radiation is associated with higher colitis and colorectal cancer incidence in IL10-/- mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5057.

Abstract A49: Using IL10-/- mouse model to assess heavy-ion radiation exposure-associated colitis and colorectal cancer incidence

Abstract Underlying risk of γ-ray-induced colitis and colorectal cancer incidence is emphasized by the studies on atom bomb survivors and also in patients undergoing radiotherapy. However, uncertainties in colitis and CRC risk prediction after exposure to high-LET space (particle) radiation exposure has not been realized due to lack of reliable in vivo data. Here we report IL10-/- mice as a suitable mouse model for assessment of colitis and CRC risk after exposure to space radiation. Male mice (n=12 mice/group) were whole-body exposed to sham-radiation, γ-rays (137Cs-source, 2.0 Gy), and 28Si-ion (300 MeV/n; 70 keV/μm; 1.4 Gy). We used γ-ray equitoxic doses using relative biologic effectiveness (RBE) values determined earlier. Mice were sacrificed 90 days after irradiation, and colon swiss rolls were prepared and histopathologic assessment of colitis score and CRC grade was noted. Further, inflammation-associated gene-expression analysis was conducted in both radiation-induced tumor and adjoining normal tissue area. Immunohistochemistry (β-catenin, Cyclin-D1, and phospho-histone H3) was also performed to assess HZE-induced proliferative signaling. Relative to controls and γ-ray, colitis score, colon tumor incidence, size, and grade were significantly higher after space (28Si-ion) radiation exposure. Additionally, tumor incidence per unit of radiation (per cGy) was also higher after 28Si-ion radiation relative to γ radiation. Higher number of phospho-histone H3-positive cells in 28Si-ion exposed mouse colon demonstrated increased proliferative index resulting in increased intestinal tumors of larger size and grade was due to greater activation of β-catenin and its downstream effector cyclin D1. Inflammatory gene signature was more pronounced after 28Si-ion exposure. Significant upregulation of GATA4, ICAM1, ITGA2, and EGFR was exclusive to 28Si-ion exposed mouse colon; however, PTGES and TGFβ1 were upregulated in both γ and 28Si-ion exposed mice. Overall, our findings suggest that IL10-/- mice are a suitable model to assess IR-induced colitis and CRC risk and space radiation carries higher risk of colitis and CRC incidence, relative to γ-rays at comparable doses. This study has implications for risk prediction in astronauts planning for deep-space missions and also for cancer patients planning to undergo particle radiotherapy. Citation Format: Shubhankar Suman, Bo-Hyun Moon, Albert J. Fornace, Jr., Kamal Datta. Using IL10-/- mouse model to assess heavy-ion radiation exposure-associated colitis and colorectal cancer incidence [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr A49.

PD42-02 LOWERING POSITIVE MARGIN RATES AT RADICAL PROSTATECTOMY BY COLOR CODING OF BIOPSY SPECIMENS TO PERMIT INDIVIDUALIZED PRESERVATION OF THE NEUROVASCULAR BUNDLES: IS IT FEASIBLE? A PILOT INVESTIGATION.

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy VI1 Apr 2018PD42-02 LOWERING POSITIVE MARGIN RATES AT RADICAL PROSTATECTOMY BY COLOR CODING OF BIOPSY SPECIMENS TO PERMIT INDIVIDUALIZED PRESERVATION OF THE NEUROVASCULAR BUNDLES: IS IT FEASIBLE? A PILOT INVESTIGATION. Wei Phin Tan, Patrick Whelan, Ritu Ghai, Shahid Ekbal, and Leslie Deane Wei Phin TanWei Phin Tan More articles by this author , Patrick WhelanPatrick Whelan More articles by this author , Ritu GhaiRitu Ghai More articles by this author , Shahid EkbalShahid Ekbal More articles by this author , and Leslie DeaneLeslie Deane More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1955AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The ability of mpMRI to distinguish extracapsular extension from organ-confined disease when a lesion in is contact with the capsule remains poor and has very limited sensitivity. We aim to evaluate whether color-coding of core biopsy specimens aid in preservation of the neurovascular bundles on radical prostatectomy, from an oncological perspective. METHODS MRI guided transrectal ultrasound and biopsy of the prostate was performed in 51 consecutive patients suspected of being high risk for harboring prostate cancer. Core specimens were labeled with blue dye at the deep aspect and red dye at the superficial peripheral aspect of the core. The distance from the tumor to the end of the dyed specimen was measured to determine if there was an area of normal tissue between the prostate capsule and tumor (figure 1). RESULTS Of the 51 patients undergoing prostate biopsy, 30 (58.8 %) were found to have cancer of the prostate. This was Grade Group 1 in 13.7 %, 2 in 25.5 %, 3 in 7.8 %, 4 in 7.8 % and 5 in 3.9 % of the cohort. A total of 461 cores were analyzed in the cohort, of which 122 showed cancer. 4 patients opted to undergo robotic assisted laparoscopic radical prostatectomy. No patients had a positive surgical margin (PSM) or extra prostatic extension (EPE) on radical prostatectomy if there was a margin of normal prostatic tissue seen between the dye and the tumor on prostate biopsy. Color coding the specimen does not alter the cellular architecture, nor does it affect the integrity of DNA/RNA material, thus having no potential for impacting genomic assessment of the tissue for further clinical risk analysis and stratification. CONCLUSIONS Color-coding of prostate biopsy core specimens assists in tailoring the approach to preservation of the neurovascular bundles without compromising early oncological efficacy. Further study is required to determine whether this simple modification of the prostate biopsy protocol is valuable in larger groups of patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e814 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Wei Phin Tan More articles by this author Patrick Whelan More articles by this author Ritu Ghai More articles by this author Shahid Ekbal More articles by this author Leslie Deane More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

JOURNAL CLUB: Evaluation of Diffusion Kurtosis Imaging of Stroke Lesion With Hemodynamic and Metabolic MRI in a Rodent Model of Acute Stroke

Diffusion kurtosis imaging (DKI) has emerged as a new acute stroke imaging approach, augmenting routine DWI. Although it has been shown that a diffusion lesion without kurtosis abnormality is more likely to recover after reperfusion, whereas a kurtosis lesion shows poor response, little is known about the underlying pathophysiologic profile of the kurtosis lesion versus the kurtosis lesion-diffusion lesion mismatch. We performed multiparametric MRI, including arterial spin labeling, pH-sensitive amide proton transfer, and DKI, in a rodent model of acute stroke caused by embolic middle cerebral artery occlusion. Diffusion and kurtosis lesions were semiautomatically segmented, and multiparametric MRI indexes were compared among the kurtosis lesion, diffusion lesion, kurtosis lesion-diffusion lesion mismatch, and the contralateral normal tissue area. We confirmed a significant difference between diffusion lesion and kurtosis lesion volumes (mean [± SD] volume, 151 ± 65 vs 125 ± 47 mm3; p < 0.05). Although ischemic lesions have significantly reduced cerebral blood flow compared with contralateral normal tissue, we did not find a significant difference in cerebral blood flow between the kurtosis lesion and the kurtosis lesion-diffusion lesion mismatch (mean cerebral blood flow, 0.53 ± 0.10 vs 0.47 ± 0.14 mL/g of tissue per minute; p > 0.05). Of importance, the pH of the kurtosis lesion was significantly lower than that of the lesion mismatch (mean pH, 6.81 ± 0.08 vs 6.89 ± 0.09; p < 0.01). The present study confirms that DKI provides an expedient approach for refining the heterogeneous DWI lesion that is associated with graded metabolic derangement, which is promising for improving the infarction core definition and ultimately helping to guide stroke treatment.

Lowering positive margin rates at radical prostatectomy by color coding of biopsy specimens to permit individualized preservation of the neurovascular bundles: is it feasible? a pilot investigation.

ABSTRACTObjective:To evaluate whether color-coding of prostate core biopsy specimens aids in preservation of the neurovascular bundles from an oncological perspective.Materials and Methods:MRI guided transrectal ultrasound and biopsy of the prostate were performed in 51 consecutive patients suspected of being at high risk for harboring prostate cancer. Core specimens were labeled with blue dye at the deep aspect and red dye at the superficial peripheral aspect of the core. The distance from the tumor to the end of the dyed specimen was measured to determine if there was an area of normal tissue between the prostate capsule and tumor.Results:Of the 51 patients undergoing prostate biopsy, 30 (58.8%) were found to have cancer of the prostate: grade group 1 in 13.7%, 2 in 25.5%, 3 in 7.8%, 4 in 7.8% and 5 in 3.9% of the cohort. A total of 461 cores were analyzed in the cohort, of which 122 showed cancer. Five patients opted to undergo robotic assisted laparoscopic radical prostatectomy. No patients had a positive surgical margin (PSM) or extra prostatic extension (EPE) on radical prostatectomy if there was a margin of normal prostatic tissue seen between the dye and the tumor on prostate biopsy.Conclusion:Color-coding of prostate biopsy core specimens may assist in tailoring the approach for preservation of the neurovascular bundles without compromising early oncological efficacy. Further study is required to determine whether this simple modification of the prostate biopsy protocol is valuable in larger groups of patients.

Vasohibin-1 as a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer

BackgroundWe previously reported high expression of vasohibin-1 (VASH1), which is specifically expressed in activated vascular endothelial cells, was a prognostic indicator of disease progression in prostate cancer. The aim of this study was to assess whether VASH1 expression at the area of normal prostatic tissue as well as that of intratumoral tissue could reflect the grade of malignancy of prostate cancer.ResultsPathological upgrade of Gleason Score ≥7 by radical prostatectomy was observed in 48 patients (upgraded group). The median VASH1 densities of the intratumoral and normal areas were 9.7 ± 9.5 and 13.3 ± 11.8, respectively, and the median MVDs were 58.6 ± 20.3 and 64.1 ± 23.5, respectively. We detected a strong positive correlation with each other for both VASH1 density (ρ = 0.589, p < 0.001) and MVD (ρ = 0.342, p < 0.001). VASH1 density was significantly higher in the upgreaded group than in the non-upgraded group regardless of prostatic location (intratumoral area: p < 0.001, normal area: p < 0.001).ConclusionsEven if the tumor volume was low in biopsy samples, VASH1 density reflected the grade of malignancy throughout the prostate. These results suggested that VASH1 expression could be a novel microenvironmental biomarker for patient risk reclassification in low-risk prostate cancer.Materials and MethodsAmong the 1177 patients who underwent radical prostatectomy, 104 patients diagnosed with Gleason Score ≤6 and positive cores ≤3 were included. We immunohistochemically examined the microvessels positive for anti-CD34 as microvessel density (MVD), and those with activated endothelial cells as VASH1 density using prostatic biopsy samples, and evaluated the association between their expressions and clinicopathological findings.

The effect of a multi-material artifact reduction algorithm in a wide-detector CT system to reduce the beam hardening artifacts in CT imaging

Objective To investigate the effect of the multi-material artifact reduction (MMAR) algorithm of wide-detector CT system in reducing the beam hardening artifacts in brain CT imaging. Methods Nine tubes with various iodine concentrations (0.1-16.0 mgI/ml) were placed in a uniform phantom filled with soft-tissue equivalent material. The phantom was scanned using different combinations of the tube voltage and current as follows: 80 kV/530 mA, 100 kV/295 mA, 120 kV/190 mA and 140 kV/135 mA. The scanning was performed using the GE Discovery 750 and GE Revolution CT scanners, respectively. The CT values and standard deviations of the uniform areas between tubes were measured. The artifact index(AI) was calculated by using the standard deviation value outside the tubes as background noise. The artifact index values under different kV/mA combinations with different scanners were compared. CT brain images of 36 patients (n=18 on Discovery CT and n=18 on Revolution CT) were randomly selected. CT values of normal brain tissue and dark bands areas in the posterior fossa were measured for each case. The AI was calculated for these cases as for the phantom study. Paired t test was performed for phantom data analysis, and independent t test was performed for the clinical cases data analysis. Results The average AI values with Revolution CT(4.96±1.39, 4.80±1.57, 4.56±1.45, 4.76±1.57) were smaller than those of Discovery 750 (11.90±6.61, 11.17±5.61, 8.85±4.59, 8.77±3.85) under different tube voltage settings (t=3.714, 4.186, 3.745, 4.634, P<0.001) . The higher the iodine concentration difference between tube pairs was, the higher the artifact index;As for clinical data, the difference in AI values between Revolution CT(2.31±0.95) and Discovery 750(3.91±1.32) was found statistically significant (t=4.066, P<0.001) . Conclusion The multi-material artifact reduction algorithm implemented on the wide-detector Revolution CT scanner can significantly reduce beam hardening artifacts. Key words: Beam hardening artifacts; Tomography, X-ray computed; Multi-material artifact reduction

Detection of cancerous kidney tissue by means of SERS spectroscopy of extracellular fluid

AbstractWe present a novel approach for detection of cancerous kidney tissue areas by measuring surface enhanced Raman scattering (SERS) spectra of extracellular fluid taken from kidney tissue. The method is based on spectral analysis of the cancerous and normal tissue areas in order to find the specific spectral markers. The samples were prepared by sliding the kidney tissue over a substrate—calcium fluoride optical window. For producing the SERS signal, the dried extracellular fluid film was covered by silver nanoparticle colloidal solution. In order to suppress fluorescence background, the measurements of the dried samples were performed in the NIR spectral region with the Raman excitation wavelength of 1,064 nm. The most significant spectral differences—spectral markers—were found in the wavenumber region between 400 and 1,800 cm−1, where spectral bands related to various vibrations of carbohydrates, amino acids, and nucleic acids are located. Spectral markers in the SERS spectra are different from those in IR absorption spectra. The SERS spectroscopic method has a potential to be used directly during the surgery.