Normal Parenchyma Research Articles

CT target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas

ObjectiveTo discuss the value of computed tomography (CT) iterative reconstruction technique combined with target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas (SPTP).MethodsThe clinical information and CT examination data of 27 patients with SPTP were retrospectively analyzed, and the general condition and CT performance of the patients were observed. The CT image reconstruction algorithm of all patients used iterative reconstruction technique combined with the application of target scanning technique.ResultsA total of 27 patients were included in this study, including 6 males and 21 females, aged 14–72 years with a mean age of 39.6 ± 13.6 years. SPTP was more common in young and middle-aged females, with a low level of tumor markers, dominated by cystic-solid tumors. The combination of CT iterative reconstruction technology and targeted scanning revealed the following: the capsule of SPTP was clear and complete, where calcifications were visible, solid components were progressively enhanced, and rare pancreatic and bile duct dilation was seen. Tumors were cystic-solid in 18 of 27 patients with SPTP, of which the solid components showed isodensity or slightly low-density, with calcifications. The solid components and cyst walls were mildly enhanced during the arterial phase, and were progressively enhanced during the parenchymal phase, portal vein phase, and delayed phase, with their enhancement degree lower than that of normal pancreatic parenchyma, and pancreatic and bile duct dilation was rare. There were no statistical differences in tumor location, morphology, growth pattern, integrity of capsule, cystic or solid, calcifications, and enhancement features between the male group and the female group (P > 0.05).ConclusionThe iterative reconstruction combined with target scanning clearly displayed the CT features of tumors, helping the diagnosis and clinical treatment of the disease.

CD70 is Consistently Expressed in Primary and Metastatic Clear Cell Renal Cell Carcinoma

BackgroundCD70 is commonly overexpressed in renal cell carcinoma and is minimally expressed in normal human tissue, making it a potential therapeutic target for patients with advanced renal cell carcinoma. The expression frequency of CD70 in metastatic renal cell carcinoma is not well established. Materials and MethodsWe assessed CD70 immunohistochemistry in 391 primary renal tumors and 72 metastatic renal cell carcinomas on a tissue microarray including 26 sets of paired primary and metastatic tumors. ResultsCD70 was frequently overexpressed in clear cell carcinoma, with a significantly lower expression rate in papillary renal cell carcinoma (P < .0001). No expression of CD70 was detected in other types of renal tumors and normal renal parenchyma. In clear cell renal cell carcinoma, CD70 expression was significantly correlated with hypoxia pathway proteins, corroborating with a recent study suggesting that CD70 is a downstream target gene of hypoxia-inducible factor. While higher expression levels were observed in males and non-Caucasians, CD70 expression was not associated with tumor grade, sarcomatoid differentiation, stage, or cancer-specific survival. Further, analysis of 26 paired primary and metastatic tumors from same individuals revealed a concordance rate of 85%. ConclusionOur findings validated CD70 as a promising therapeutic target for patients with metastatic clear cell renal cell carcinoma. The utility of primary tumor tissue as surrogate samples for metastatic clear cell carcinoma awaits future CD70-targeted clinical trials.

10000-SPE-1 STEM CELL-BASED GENE THERAPY FOR MALIGNANT GLIOMA USING GENOME-EDITED HUMAN INDUCED PLURIPOTENT STEM CELLS

Abstract Glioblastoma is the most aggressive primary brain tumor, and is characterized by diffuse infiltration into the normal brain parenchyma. New therapeutic approaches targeting invasive biological behaviour are warranted. In the present study, we show that neural stem cells (NSCs) derived from CRISRP/Cas9-edited induced pluripotent stem cells (iPSCs) have high tumor-trophic migratory capacity and stable constitutive therapeutic transgene expression, which leads to strong anti-tumor effects against glioma stem cell (GSC) models. The present study provides answers to some important research questions associated with stem cell-based gene therapy. First, the tumor-trophic migratory capacities of human iPSC-derived NSCs (iPSC-NSCs), fetal NSCs, and mesenchymal stem cells (MSCs) were quantitatively evaluated by spatiotemporal methodologies. We demonstrated that iPSC-NSCs have a higher tumor-trophic migratory capacity than MSCs in the brain. Self-repulsive action and pathotropism were important for the migration of iPSC-NSCs: ephrin ligand/receptor mediated repulsion of iPSC-NSCs and CXCL12-CXCR4 interactions between GSCs and iPSC-NSCs. Second, a prodrug converting enzyme fusion gene was selected as a therapeutic gene in human iPSCs. In general, stable constitutive transgene expression by viral vectors was difficult in human iPSCs. Furthermore, viral vectors integrate randomly into the host genome, which raises concerns about transgene silencing, insertional mutagenesis, and oncogene activation. In the present study, several common insertion sites including GAPDH, ACTB, and AAVS1, were compared. The most appropriate gene locus that achieved stable constitutive transgene expression was determined via CRISPR/Cas9-mediated genome editing. Third, we revealed the novel mechanism of action using iPSC-NSCs expressing CD-UPRT, in which ferroptosis was associated with enhanced anti-tumor immune responses. We demonstrated that the established iPSC-NSCs had strong therapeutic efficacy in GSC animal models. Finally, predictive biomarkers for the efficacy of the present treatment strategy were established. We will conduct a clinical trial of this treatment strategy. This research concept can disseminate biological, medical and engineering advances.

Thoracoscopic precision excision technique for small lung lesions using radiofrequency identification marking.

With the introduction of multi-detector computed tomography (CT), the number of incidentally detected small lung nodules has dramatically increased. Determination of lung nodule malignancy is crucial, and an early diagnosis of these indeterminate lesions can lead to subsequent potentially curative treatment. However, there are some limitations to excising these nodules with sublobar resection in a minimally invasive thoracoscopic setting. Under thoracoscopy, although stapler-based wedge resection seems to be the preferred technique, particularly in patients whose lesions are located far from the edge of the lobe, the stapler can unexpectedly sacrifice normal pulmonary parenchyma. To overcome this issue, we have developed a wireless excision precision technique using cone-beam CT-guided electromagnetic navigation bronchoscopy in a minimally invasive thoracoscopic setting. Our technique is implemented in a hybrid operating room, and small tumors can be removed using a radiofrequency identification microchip without intraoperative fluoroscopy and do not require lung palpation under thoracoscopy.

Lung ultrasound and high-resolution computed tomography quantitative variations during nintedanib treatment for systemic sclerosis-associated interstitial lung disease.

Lung ultrasound (LUS) and high-resolution CT (HRCT) are commonly used for the evaluation of interstitial lung disease (ILD). Nintedanib (NIN) is an antifibrotic therapy approved for systemic sclerosis-associated ILD (SSc-ILD). We assessed LUS and quantitative HRCT changes in SSc-ILD patients treated with NIN during a 1 year follow-up, evaluating relationships between imaging variations and functional or quality-of-life outcomes. SSc-ILD patients who started NIN were enrolled and followed for 12 months. Pulmonary function tests and patient-reported outcome measures (PROMs) were assessed half-yearly and quarterly, respectively. LUS was performed quarterly evaluating the presence of B-lines (BL) and pleural line irregularities (PLI). HRCT was repeated after 1 year and quantitatively analysed with CALIPER software. Ten patients (70% female, mean age 62 years) were enrolled. The mean total number of both BL and PLI was constantly decreased during NIN treatment, being significantly reduced after 12 months (from 175.1 [66.7] to 120.8 [70.3] for BL, P = 0.005; and from 50.6 [32.5] to 37.2 [22.4] for PLI, P = 0.05). Male gender, smoking habit and baseline forced vital capacity <70% predicted were associated with worse LUS outcomes. A greater reduction in both BL and PLI was observed in those who improved in PROMs, especially modified Medical Research Council dyspnoea scale (P = 0.016 and P = 0.04, respectively) and Saint George's Respiratory Questionnaire (P = 0.006 and P = 0.026, respectively). No significant changes in the CALIPER percentages of normal parenchyma or ILD elements were observed after 12 months of NIN, thus paralleling the stabilization obtained at pulmonary function tests. We present preliminary results on NIN effects on SSc-ILD as assessed by LUS, a useful method for frequently repeated monitoring, and CALIPER, a valid implementation whenever a HRCT is performed.

Abstract LB_C05: A novel approach to convert non-resectable pancreatic cancer with major artery involvement using endovascular activation of Padeliporfin by vascular-targeted photodynamic therapy

Abstract Pancreatic cancer is a fatal disease: the patient usually has a very poor prognosis and limited treatment options. It is projected to be the second leading cause of cancer-related death by 2030. It is estimated that 80% of patients have metastatic or localized disease with vascular involvement at presentation, not amenable to surgery. Thus, a therapy that will convert unresectable, due to vascular involvement, tumors to resectable is an unmet medical need. We developed a novel treatment relying on endovascular activation of a photosensitizer Padeliporfin, by a vascular-targeted photodynamic therapy (VTP) to clear the artery from the encasing tumor enabling surgery. Padeliporfin is administered intravenously and activated locally by illumination via an optical fiber, deployed within the tumor encased artery by an angioplasty procedure under fluoroscopy. In a proof-of-concept study in normal swine model, treatment induced areas of ablation in normal pancreatic parenchyma while sparing the artery and other major structures in it’s vicinity. Drug and light doses used were proved effective in other solid tumors in preclinical and clinical studies. Safety was evaluated in a controlled study comprised of 12 pigs subjected to Padeliporfin VTP in a superior mesenteric artery (SMA). Two light doses were tested. Control groups received no drug or no illumination and drug. Follow up was 48 hours or seven days post treatment. Clinical observations and blood test results did not reveal any signs of decreased wellness without differences between treated and control groups. Lipase results were unchanged compared to the baseline. Amylase levels were within the normal range in all animals. Histopathology findings 48 hours post VTP in the SMA and surrounding tissues were similar in treated and control animals. Observed changes were manifested as small lesions consistent with angioplasty procedure impact, involving less than 25% of the media circumference. Small foci of coagulative necrosis were observed in the pancreatic parenchyma in the vicinity of SMA. In the seven-day samples, there was media pressure necrosis in occasional sections of the artery in all groups involving less than 25% of the circumference, attributed to the angioplasty procedure. Minimal fibrosis in a few samples, consisted of focal areas of fibroblast proliferation, indicating early regeneration, with no architectural or thickness changes of the arterial wall. The tissues surrounding SMA as well as organs downstream to the treated artery were mostly within normal ranges. Our results demonstrate that endovascular Padeliporfin VTP is feasible and has an acceptable safety profile together with evidence of ability to ablate pancreatic tumors encasing major abdominal arteries. The efficacy is further supported by our studies showing effective tumor ablations in orthotopic mouse models especially in combination with immune modulating therapies. A phase I trial (NCT5918783) aims to evaluate the potential of this approach for converting unresectable pancreatic cancer patients to amenable for surgery. Citation Format: Dina Preise, Yaniv Cohen, Genia Alpert, Zachary Sacks, Tamar Yechezkel, Natalia Kudinova, Eyal Morag, Ehud Willenz, Julia Rothman, Keren Brook, Inna Krasnopolskaya, Lilach Agemy, Sofia Zilber, Hooman Yarmohammadi, David Kelsen, David Perry, Avigdor Scherz. A novel approach to convert non-resectable pancreatic cancer with major artery involvement using endovascular activation of Padeliporfin by vascular-targeted photodynamic therapy [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_C05.

Evaluation of the role of diffusion-weighted imaging in various pancreatic pathologies

Background: Diffusion-weighted imaging (DWI) can confidently characterize the nature of a lesion. “Apparent diffusion coefficient” (ADC) has a role in evaluating malignant lesions of the pancreas when conventional sequences appear normal. Aims and Objectives: The aim of the study was to determine the role of DWI and ADC to differentiate benign from malignant pancreatic lesions. Materials and Methods: An observational study was carried out on 75 participants with a suggestion of pancreatic pathologies at a tertiary care institute. Twenty-five participants, who had normal parenchyma of the pancreas, were taken as controls. Magnetic resonance imaging protocol was done, including DWI and ADC. Data analysis was done using coGuide software. ADC was the primary outcome of interest. Results: Out of the 75 cases, 76.9 % (n=60) were males. 15.4 % (n=9) of pathologies were malignant. A significant decrease of ADC values in subjects with acute diffuse pancreatitis (1.12×10-3), acute on chronic pancreatitis (1.14×10-3), chronic pancreatitis (1.32×10-3) as well as adenocarcinoma pancreas (0.92×10-3) was seen in comparison to the controls (1.41×10-3). ADC values for acute pancreatitis, chronic pancreatitis, and acute on chronic pancreatitis were significantly higher than malignancy. Conclusion: DWI and ADC is a useful tools complementing conventional MR imaging and other imaging modalities in characterizing pancreatic pathologies. Mean ADC values of various pancreatic diseases can be determined without major overlap and a reasonable cutoff value can be obtained for differentiating benign and malignant lesions.

Primary Renal Well Differentiated Neuroendocrine Neoplasm with Nodal Metastasis Possibly Originating from A Teratoma

Abstract Introduction/Objective Well differentiated neuroendocrine tumors (WDNETs) of the kidney are extremely rare and are aggressive tumors with higher rate of metastasis, even those with low proliferative rates. Primary WDNET arising in a renal teratoma is an exceedingly rare entity. Methods/Case Report Herein, we describe a case with a primary WDNET and possible mature cystic teratoma of the right kidney of a 22-year old male who presented with an epigastric/right upper quadrant abdominal pain. Abdominal MRI identified a 4.4cm isointense mass in the mid-lower pole of the right kidney within renal sinus. Robotic assisted partial nephrectomy was performed. Grossly, the 56gm excised mass is well circumscribed with tan- brown friable homogeneous cut surface. Histologically, tumor cells show round to oval nuclei with speckled chromatin and calcifications. The tumor metastasized to two hilar lymph nodes. The tumor is positive for AE1/AE3, vimentin, synaptophysin, CD99, INI-1 (SMARCB1), FLI-1, and chromogranin. While negative for CK7, CK20, PAX-8, CD10, WT-1, CEA, and CDX-2. Ki-67 is 2% and the mitotic count is &amp;lt; 1 per 10 HPF. The histology and immunoprofile are consistent with WDNET. No pathogenic fusions detected on Next Generation Sequencing (NGS) targeting RNA and DNA panels. Adjacent to the tumor, there is a cystic structure lined by intestinal mucosa positive for CDX2. Results (if a Case Study enter NA) N/A Conclusion Neuroendocrine cells are not identified in the normal parenchyma of the kidney, while noted in adjacent intestinal mucosa raising the possibility that renal WDNET is arising from mature renal teratoma.

Analysis of MRI features of hepatocyte nuclear factor 1α-inactivated hepatocellular adenoma

Objective: To investigate the MRI imaging features of hepatocyte nuclear factor 1α- inactivated hepatocellular adenoma (H-HCA). Methods: Clinical data and MRI images of 19 H-HCA cases who were pathologically confirmed at Zhongshan Hospital Affiliated to Fudan University between August 2014 and July 2020 were retrospectively analyzed. Among them, there were 15 females and 4 males, aged 16-47 (32± 7) years old. Tumor number, location, shape, size, boundary, MRI plain scan signal intensity, dynamic enhancement features of each phase, presence or absence of intratumoral fat content, pseudocapsule, and others were analyzed. The differences in apparent diffusion coefficient (ADC) values between the lesion and the surrounding normal liver parenchyma were compared for statistical significance. t-test was used for statistical analysis. Results: There were a total of 24 lesions in 19 cases. 14 cases had solitary lesions, and five cases had multiple lesions. 15 and nine lesions were located in the right and left lobes of the liver, respectively. 20 lesions were round or quasi-round, and four were irregular or lobulated. The tumor's maximal diameter was 0.6-8.6 (3.5 ± 2.4) cm. T(1)-weighted image (WI) showed hyperintense to iso-intense signals in 20 lesions and hypointense signals in four. T(2)WI showed iso-to-slightly high signal intensity in 16 lesions, with two hyperintense and six hypointense signals. Diffusion-weighted image (DWI) revealed hyperintense to iso-intense signals. Lesions mean ADC value was (1.289 ± 0.222)×10(-3) mm(2)/s, while the adjacent normal liver parenchyma's mean ADC value was (1.307 ± 0.236)×10(-3) mm(2)/s, with no statistically significant difference between the two (P > 0.05). During the arterial phase, 15 of the 18 lesions that underwent dynamic contrast-enhanced scanning with gadoxetate disodium (Gd-DTPA) were mildly to moderately enhanced and three were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the delayed phase showed a hypointense signal. During the arterial phase, two of the six lesions scanned by gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid ((Gd-EOB-DTPA) dynamic enhancement were mildly to moderately enhanced, while four were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the transition and hepatobiliary-specific phases showed hypointense signals. Intracellular steatosis occurred in 21 lesions, of which 19 were diffuse steatosis and 16 formed pseudocapsules in the delayed phase. Conclusion: H-HCA often occurs in young females as solitary lesions and has certain MRI features. T1WI anti-phase diffuse signal reduction and post-enhanced hypovascular withdrawal enhancement patterns can aid in accurately diagnosing the disease condition.

Spatially distinct molecular patterns of gene expression in idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a heterogeneous disease that is pathologically characterized by areas of normal-appearing lung parenchyma, active fibrosis (transition zones including fibroblastic foci) and dense fibrosis. Defining transcriptional differences between these pathologically heterogeneous regions of the IPF lung is critical to understanding the distribution and extent of fibrotic lung disease and identifying potential therapeutic targets. Application of a spatial transcriptomics platform would provide more detailed spatial resolution of transcriptional signals compared to previous single cell or bulk RNA-Seq studies.MethodsWe performed spatial transcriptomics using GeoMx Nanostring Digital Spatial Profiling on formalin-fixed paraffin-embedded (FFPE) tissue from 32 IPF and 12 control subjects and identified 231 regions of interest (ROIs). We compared normal-appearing lung parenchyma and airways between IPF and controls with histologically normal lung tissue, as well as histologically distinct regions within IPF (normal-appearing lung parenchyma, transition zones containing fibroblastic foci, areas of dense fibrosis, and honeycomb epithelium metaplasia).ResultsWe identified 254 differentially expressed genes (DEGs) between IPF and controls in histologically normal-appearing regions of lung parenchyma; pathway analysis identified disease processes such as EIF2 signaling (important for cap-dependent mRNA translation), epithelial adherens junction signaling, HIF1α signaling, and integrin signaling. Within IPF, we identified 173 DEGs between transition and normal-appearing lung parenchyma and 198 DEGs between dense fibrosis and normal lung parenchyma; pathways dysregulated in both transition and dense fibrotic areas include EIF2 signaling pathway activation (upstream of endoplasmic reticulum (ER) stress proteins ATF4 and CHOP) and wound healing signaling pathway deactivation. Through cell deconvolution of transcriptome data and immunofluorescence staining, we confirmed loss of alveolar parenchymal signals (AGER, SFTPB, SFTPC), gain of secretory cell markers (SCGB3A2, MUC5B) as well as dysregulation of the upstream regulator ATF4, in histologically normal-appearing tissue in IPF.ConclusionsOur findings demonstrate that histologically normal-appearing regions from the IPF lung are transcriptionally distinct when compared to similar lung tissue from controls with histologically normal lung tissue, and that transition zones and areas of dense fibrosis within the IPF lung demonstrate activation of ER stress and deactivation of wound healing pathways.

Speaking of the "Devil": Diagnostic Errors in Interstitial Lung Diseases.

Interstitial lung diseases are respiratory diseases, which affect the normal lung parenchyma and can lead to significant pulmonary fibrosis, chronic respiratory failure, pulmonary hypertension, and ultimately death. Reuniting more than 200 entities, interstitial lung diseases pose a significant challenge to the clinician, as they represent rare diseases with vague and insidious respiratory symptoms. As such, there are many diagnostic errors that can appear along the journey of the patient with ILD, which leads to significant delays with implications for the prognosis and the quality of life of the patient.

RADT-26. IMPROVING RADIATION TARGET VOLUME DEFINITION FOR GLIOBLASTOMA USING PREDICTIONS OF TUMOR RECURRENCE FROM MACHINE LEARNING AND PRE-RADIOTHERAPY ADVANCED MRI

Abstract INTRODUCTION Standard-of-care (SOC) radiation therapy (RT) planning only utilizes a fairly 1.5-2cm uniform expansion of T2-weighted-FLAIR MRI lesion to generate a clinical target volume (2cm-CTV), without considering the spatial heterogeneity and infiltrative nature of glioblastomas. This study aimed to use multi-parametric MRI with 2 artificial intelligence (AI)-based approaches to predict regions of subsequent tumor progression and compare the resulting predictions to the 2cm-CTV, with the hypothesis that applying deep learning will lead to improved detection of subclinical disease that is under-treated, and more accurately delineate areas at higher risk for progression, than the uniform 2cm-CTV. METHODS We used normalized maps of anatomical, diffusion, and metabolic MRI post-surgical resection and before RT and chemotherapy from 72 patients newly-diagnosed with glioblastoma to train Random-Forest and deep-learning UNet models to identify voxels that later exhibit progression by either the contrast-enhancing-lesion (CEL) or T2-lesion (T2L). All models were trained/validated on 54 and tested on 18 patients after careful inter-exam alignment and normalization. Model performance was compared to the 2cm-CTV using a Progression-Coverage-Coefficient (PCC), a weighted Dice coefficient that accounts for tumor-size. RESULTS Random-Forest models were able to predict subsequent contrast-enhancing (CE) and T2 non-enhancing (NE) progression with an average respective test AUC of 0.88 and 0.82, with 15.6%/9.6% higher performance on patients who progressed early. The 2cm-CTV treatment plan achieved the highest sensitivity (0.833 vs 0.795) but also the lowest specificity (0.879 vs 0.935), over-treating normal-appearing-brain. Our deep learning model outperformed the 2cm-CTV in covering the progressed lesion, with the highest specificity (0.935 vs 0.879), PCC (0.741 vs 0.734), and had comparable sensitivity (0.795) to the 2cm-CTV, while sparing more normal brain compared to the 2cm-CTV. CONCLUSION This study demonstrates the potential benefit of using multi-parametric MRI with deep learning to assist in RT treatment planning to reduce excessive treatment of normal brain parenchyma.

5-aminolevulinic acid-guided endoscopic biopsy with violet light-emitting diode flashlight in malignant glioma: Technical note.

5-aminolevulinic acid (5-ALA) photodynamic diagnosis (PDD) has enabled better identification of malignant tumor cells and real-time intraoperative guidance. Here, we report a reasonable procedure for 5-ALA-guided endoscopic biopsy with a violet light-emitting diode (LED) flashlight for deep-seated malignant gliomas. A 63-year-old man presented with a headache and left upper homonymous quadrantanopia. Imaging studies showed atypical lesions with non-significant and partial contrast enhancement in the right deep temporo-occipital lobe. An endoscopic biopsy was performed under the guidance of 5-ALA PDD with a violet LED flashlight. The tumor tissues, which were difficult to distinguish from normal brain parenchyma under white light, were positive for 5-ALA fluorescence. The histopathological diagnosis was astrocytoma (the World Health Organization grade 3). The patient underwent adjuvant chemoradiation therapy. Headache and anopia improved, and no recurrence was observed at 12 months follow-up. This technique of neuroendoscopic biopsy guided by 5-ALA PDD fluorescence with a violet LED flashlight may allow a safe and accurate diagnosis of deep-seated malignant gliomas.

NIMG-70. TRACKING CELLULAR SOCIAL BEHAVIOR OF PATIENT-DERIVED PRIMARY CELL LINES TO GATHER NEW INSIGHTS FOR BETTER STRATIFICATION OF GLIOBLASTOMA PATIENTS

Abstract Glioblastoma is one of the most frequent and aggressive brain tumors. The average life of these patients is on average less than 15 months, due to the proliferation and invasiveness of the tumor cells, which not only constitute the tumor mass but which also infiltrate the normal parenchyma brain to form new cancerous sites. Knowing the specific behavior of the cell types that make up the tumor of every single patient, in terms of volume, shape, motility, and cell-cell interaction could be informative for patients’ tumor stratification. Here we developed a protocol that integrates imaging and image processing algorithms, to accurately and quantitatively identify the morphological and behavioral characteristics of tumor cells cultured in vitro and track their movement over time. This approach enables quantifying important biological processes such as cell migration and cell growth, both of which play a major role in the development of diseases. The cell tracking method combines segmentation methods with spatiotemporal optimization to analyze microscopy images. The method also determines various information about cell movements such as movement paths, speed, and distance covered. Knowing the behavior of the malignant glioma cells of a specific patient, in terms of shape and motility (e.g. direction and speed of movement), also in relation to other cells could be informative in the context of dynamic precision medicine. In this context, we created a model that integrates the characteristics of each patient's tumor cells and provides a new way of stratifying patients that can be correlated with clinical data.

Role of Permeability Surface Area Product in Grading of Brain Gliomas using CT Perfusion.

Purpose The aim of this study was to evaluate the role of permeability surface area product in grading brain gliomas using computed tomography (CT) perfusion Materials and Methods CT perfusion was performed on 33 patients with brain glioma diagnosed on magnetic resonance imaging. Of these, 19 had high-grade glioma and 14 had low-grade glioma on histopathological follow-up. CT perfusion values were obtained and first compared between the tumor region and normal brain parenchyma. Then the relative values of perfusion parameters were compared between high- and low-grade gliomas. Cut-off values, sensitivity, specificity, and strength of agreement for each parameter were calculated and compared subsequently. A conjoint factor (permeability surface area product + cerebral blood volume) was also evaluated since permeability surface area product and cerebral blood volume are considered complimentary factors for tumor vascularity. Results All five perfusion parameters namely permeability surface area product, cerebral blood volume, cerebral blood flow, mean transit time, and time to peak were found significantly higher in the tumor region than normal brain parenchyma. Among these perfusion parameters, only relative permeability surface area product and relative cerebral blood volume were found significant in differentiating high- and low-grade glioma. Moreover, relative permeability surface area product was significantly better than all other perfusion parameters with highest sensitivity and specificity (97.74 and 100%, respectively, at a cut-off of 9.0065). Relative permeability surface area product had a very good agreement with the histopathology grade. The conjoint factor did not yield any significant diagnostic advantage over permeability surface area product. Conclusion Relative permeability surface area product and relative cerebral blood volume were helpful in differentiating high- and low-grade glioma; however, relative permeability surface area product was significantly better than all other perfusion parameters. Grading brain gliomas using relative permeability surface area product can add crucial value in their management and prognostication; hence, it should be evaluated in the routine CT perfusion imaging protocol.

Partial ectopic posterior pituitary

Ectopic posterior pituitary is one of the leading causes of pituitary dwarfism related to a growth hormone deficiency. It can be either isolated or associated to other abnormalities, the most widely known being the pituitary stalk interruption syndrome [1]. Although it is a rare entity, partial ectopy consists of the coexistence of both an orthotopic and an ectopic posterior pituitary gland [2,3] (Figure 1A). It appears as a T1 hyperintensity or bright spot at the posterior sellae, consistent with the normally expected neurohypophysis [4]. A second midline bright spot located in the infundibulum (Figure 1B), or above the optic chiasm or at the floor of the third ventricle is considered the ectopic posterior pituitary gland. It features high T1 signal intensity with and without fat suppression, making it easy to distinguish from a lipoma or a supra sellar dermoid with lipid content. Contrast enhancement is similar to the normal pituitary parenchyma (Figure 1C).

Quantitative diffusion weighted imaging in patients with hepatocellular carcinoma: effects of simultaneous multi-slice acceleration and gadoxetic acid administration.

To investigate whether simultaneous multi-slice (SMS) acceleration and gadoxetic acid administration affect the quantitative apparent diffusion coefficient (ADC) and signal-to-noise ratio (SNR) measurement of DWI in patients with HCC. This prospective study initially enrolled 208 patients with clinically suspected HCC. Free breathing SMS-DWI and conventional DWI (CON-DWI) were performed before and after gadoxetic acid administration. Lesion conspicuity, ADCs and SNRs of the HCC lesion and normal liver parenchyma were independently measured by two radiologists. The paired t test or Wilcoxon signed rank test was used to evaluate the differences of lesion conspicuity, ADCs and SNRs between SMS-DWI and CON-DWI, as well as those before and after gadoxetic acid administration. A total of 102 HCC patients (90 men and 12 women; mean age, 54.6 ± 11.7 years) were finally included for analysis. SMS-DWI and CON-DWI demonstrated comparable lesion conspicuity (P = 0.081-0.566). For the influence of SMS acceleration, the SNRs of liver parenchyma on enhanced SMS-DWI were significantly higher than enhanced CON-DWI (P = 0.015). For the influence of gadoxetic acid administration, the mean ADCs were significantly higher on enhanced SMS-DWI than unenhanced SMS-DWI (HCC, P = 0.013; liver parenchyma, P = 0.032). Quantitative ADC measurements of HCC and liver parenchyma were not affected by SMS acceleration, and SMS-DWI can provide higher SNR than CON-DWI. However, the ADC measurements can be affected by gadoxetic acid administration on SMS-DWI, so it is recommended to perform SMS-DWI before gadoxetic acid administration.

An Unusual Cause of Bilateral Adrenal Incidentaloma: A Case Report of Primary Adrenal Lymphoma

Primary adrenal lymphoma (PAL) is an extremely rare among the causes of adrenal incidentaloma. Most were diagnosed with adrenal insufficiency and B symptoms (unexplained weight loss, night sweats, fever). This article presented a 57-year-old woman who was investigated for bilateral adrenal masses found incidentally on computed tomography (CT). Physical examination and laboratory tests revealed no evidence of adrenal insufficiency or B symptoms. Only 24-hour urinary metanephrine and normetanephrine excretion were increased. Tumour F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) scan showed the greatest dimension was 14 cm in the left adrenal mass and the maximum standardized uptake value (SUV max) was 26.1 (relative to mean SUV in the normal liver parenchyma, which was 2). An adrenal biopsy was performed after taking adequate precautions against the possibility of a catecholamine crisis. Histopathology revealed high-grade B-cell lymphoma. Bone marrow involvement and brain metastasis were not observed. She received the R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) regimen and intrathecal methotrexate therapy as central nervous system prophylaxis. The patient responded well to treatment, and close clinical follow-up continues. PAL should always be considered when a bilateral adrenal mass is detected.

HCV treatment outcome depends on SNPs of IFNL3-Gene polymorphisms (rs12979860) and cirrhotic changes in liver parenchyma

Background and objectiveThe allelic discrimination of IFNL3-(rs12979860 C > T) polymorphism reveals ambiguous associations with the effectiveness of oral HCV treatment. Solitary intra peripheral-blood-mononuclear-cells (PBMCs) HCV-RNA antisense-strands are independently detected in naïve and experienced cases regardless of viremia or hepatic-parenchymal alterations. We examined the frequencies of IFNL3-genetic variants with chronic-HCV-induced liver changes during the sustained virologic response (SVR) by evaluating the PBMCs- HCV-PCR after oral antiviral therapy. Methods: Twelve weeks after finishing oral antiviral therapy, the effects of IFNL3-genetic variants were evaluated in three groups of patients: Group-I (n = 25) showed HCV-RNA negativity in both serum and PBMCs-, group II (n = 52) showed positivity of HCV-RNA in PBMCs, and group-III (n = 25) had positive HCV-RNA in serum. The genetic variants of the IFNL3-gene were estimated for all the enrolled cases and correlated with their hepatic image changes. Results: IFNL3-(rs12979860) genotyping in post-direct acting antivirals (DAAs) SVR and HCV-relapse revealed: a) high frequency of CC-genotype and C-allele in group I compared to group II (P < 0.005) and group III(P ≤ 0.05) when hepatic-parenchyma looks normal by ultrasound b) frequent CT-genotype and T-allele in group II compared with I(P < 0.01) and III(P < 0.05) when liver tissues are bright (early cirrhotic-changes) c) frequent TT-genotype and T-allele in group III relative to I (P < 0.05) and II (P ≤ 0.08) when liver-tissues appear coarse by ultrasound. Conclusion: Outcomes of HCV treatment depend on host IFNL3-gene polymorphism and hepatic-parenchymal changes. A high frequency of wild-CC-genotype and C-allele is observed in patients with normal hepatic parenchyma and that achieved SVR. Solitary relapse in PBMCs occurs on increasing CT-genotype frequency when liver tissues are bright. Serologic relapse is detected when TT-genotype and T-allele are dominant in association with the cirrhotic liver. Therefore, IFNL3-gene-SNP analysis as a genetic predictor in relation to ultra-sonographic hepatic-parenchymal changes could be valuable for selecting the patients with the highest priority for treatment.

Acoustic Radiation Force Impulse (ARFI) Elastography of Focal Splenic Lesions: Feasibility and Diagnostic Potential.

Nontraumatic focal splenic lesions (FSL) are rare, and the need for tissue diagnosis must be weighed against the very high risk of bleeding after a splenic biopsy. The aim of this study was to explore the feasibility and diagnostic potential of acoustic radiation force impulse (ARFI) elastography as a noninvasive method for different benign and malignant FSLs. No human studies on the elastographic characteristics of FSL exist. This was a retrospective analysis of 34 patients with FSLs, who underwent abdominal B-mode ultrasound (B-US), contrast-enhanced ultrasound (CEUS), and standardized ARFI examinations between October 2021 and December 2022 at our university hospital. The inclusion criteria were: (i) FSL size ≥ 1 cm; (ii) 10 valid ARFI measurements of the FSL, as well as of the normal splenic parenchyma (NSP) as an in vivo reference; and (iii) diagnostic confirmation of FSL etiology based on histological examination (8/34; 23.5%) or clinical evaluation, which included a clinical and sonographic follow-up (FU), CEUS morphology, and/or morphology on cross-sectional imaging (26/34; 76.5%). CEUS was performed on all patients and the FSLs were classified according to the current guidelines; cross-sectional imaging was available for 29/34 (85.3%). The mean FU duration was 25.8 ± 30.5 months. The mean ARFI velocity (MAV) of the FSL (MAVL), the NSP (MAVP), and the ratio of the MAVL to the MAVP (MAVL/P) were calculated and compared. Of the 34 FSLs, 13 (38.2%) were malignant (mFSL) and 21 (61.8%) were benign (bFSL). The MAVL of all 34 FSLs (2.74 ± 0.71 m/s) was lower than the MAVP (3.20 ± 0.59 m/s), p = 0.009, with a mean MAVL/P ratio of 0.90 ± 0.34. No significant differences in the MAVL were observed between the mFSL (2.66 ± 0.67 m/s) and bFSL (2.79 ± 0.75 m/s). There were also no significant differences between the MAVP in patients with mFSL (3.24 ± 0.68 m/s) as compared to that in the patients with bFSL (3.18 ± 0.55 m/s). Likewise, the MAV L/P ratio did not differ between the mFSL (0.90 ± 0.41 m/s) and bFSL (0.90 ± 0.30 m/s) groups. ARFI elastography is feasible in evaluating the stiffness of FSLs. The lesions' stiffness was lower than that of the NSP, regardless of the FSL etiology. However, differentiation between benign and malignant FSL with the help of this elastographic method does not appear possible. Larger prospective studies are needed to validate these findings.