Validation of automatically measured T1 map cortico-medullary difference (ΔT1) for eGFR and fibrosis assessment in allograft kidneys.

MRI T1-mapping is an important non-invasive tool for renal diagnosis. Previous work shows that ΔT1 (cortex-medullary difference in T1) has significant correlation with interstitial fibrosis in chronic kidney disease (CKD) allograft patients. However, measuring cortico-medullary values by manually drawing ROIs over cortex and medulla (a gold standard method) is challenging, time-consuming, subjective and requires human training. Moreover, such subjective ROI placement may also affect the work reproducibility. This work proposes a deep learning-based 2D U-Net (RCM U-Net) to auto-segment the renal cortex and medulla of CKD allograft kidney T1 maps. Furthermore, this study presents a correlation of automatically measured ΔT1 values with eGFR and percentage fibrosis in allograft kidneys. Also, the RCM U-Net correlation results are compared with the manual ROI correlation analysis. The RCM U-Net has been trained and validated on T1 maps from 40 patients (n = 2400 augmented images) and tested on 10 patients (n = 600 augmented images). The RCM U-Net segmentation results are compared with the standard VGG16, VGG19, ResNet34 and ResNet50 networks with U-Net as backbone. For clinical validation of the RCM U-Net segmentation, another set of 114 allograft kidneys patient's cortex and medulla were automatically segmented to measure the ΔT1 values and correlated with eGFR and fibrosis. Overall, the RCM U-Net showed 50% less Mean Absolute Error (MAE), 16% better Dice Coefficient (DC) score and 12% improved results in terms of Sensitivity (SE) over conventional CNNs (i.e. VGG16, VGG19, ResNet34 and ResNet50) while the Specificity (SP) and Accuracy (ACC) did not show significant improvement (i.e. 0.5% improvement) for both cortex and medulla segmentation. For eGFR and fibrosis assessment, the proposed RCM U-Net correlation coefficient (r) and R-square (R2) was better correlated (r = -0.2, R2 = 0.041 with p = 0.039) to eGFR than manual ROI values (r = -0.19, R2 = 0.037 with p = 0.051). Similarly, the proposed RCM U-Net had noticeably better r and R2 values (r = 0.25, R2 = 0.065 with p = 0.007) for the correlation with the renal percentage fibrosis than the Manual ROI results (r = 0.3, R2 = 0.091 and p = 0.0013). Using a linear mixed model, T1 was significantly higher in the medulla than in the cortex (p<0.0001) and significantly lower in patients with cellular rejection when compared to both patients without rejection and those with humoral rejection (p<0.001). There was no significant difference in T1 between patients with and without humoral rejection (p = 0.43), nor between the types of T1 measurements (Gold standard manual versus automated RCM U-Net) (p = 0.7). The cortico-medullary area ratio measured by the RCM U-Net was significantly increased in case of cellular rejection by comparison to humoral rejection (1.6 +/- 0.39 versus 0.99 +/- 0.32, p = 0.019). In conclusion, the proposed RCM U-Net provides more robust auto-segmented cortex and medulla than the other standard CNNs allowing a good correlation of ΔT1 with eGFR and fibrosis as reported in literature as well as the differentiation of cellular and humoral transplant rejection. Therefore, the proposed approach is a promising alternative to the gold standard manual ROI method to measure T1 values without user interaction, which helps to reduce analysis time and improves reproducibility.

Real-time, single breath-hold, multi-slice, 2D cine radial MR image reconstruction using sc-GROG k-t ESPIRiT.

Background:Multi-slice, multiple breath-hold ECG-gated 2D cine MRI is a standard technique for evaluating heart function and restricted to one or two images per breath-hold. Therefore, the standard cine MRI requires long scan time and can result in slice-misalignments because of various breath-hold locations in the multiple acquisitions.Methods:This work proposes the sc-GROG based k-t ESPIRiT with Total Variation (TV) constraint (sc-GROG k-t ESPIRiT) to reconstruct unaliased cardiac real-time cine MR images from highly accelerated whole heart multi-slice, single breath-hold, real-time 2D cine radial data acquired using the balanced steady-state free precession (trueFISP) sequence in 8 patients. The proposed method quality is assessed via Artifact Power (AP), Root-Mean Square Error (RMSE), Structure Similarity Index (SSIM), Peak Signal-to-Noise Ratio (PSNR), blood-pool to myocardial Contrast-to-Noise-Ratio (CNR), Signal-to-Noise-Ratio (SNR) and spatial-temporal intensity plots through the blood-myocardium boundary. The proposed method quantitative results are compared with the NUFFT based k-t ESPIRiT with Total Variation (TV) constraint (NUFFT k-t ESPIRiT) approach. Furthermore, clinical analysis and function quantification are assessed by Bland-Altman (BA) analyses.Results:As supported by the visual assessment and evaluation parameters, the reconstruction results of the sc-GROG k-t ESPIRiT approach provide an average 21%, 12%, 1% and 47% improvement in AP, RMSE, SSIM and PSNR, respectively in comparison to the NUFFT k-t ESPIRiT approach. Furthermore, the proposed method gives on average 45% and 58% improved blood-pool to myocardial CNR and SNR than the NUFFT k-t ESPIRiT approach. Also, from the BA plot, the proposed method gives better left ventricular and right ventricular function measurements as compared to the NUFFT k-t ESPIRiT scheme.Conclusions:The sc-GROG k-t ESPIRiT (Proposed Method) improves the spatio-temporal quality of the whole heart multi-slice, single breath-hold, real-time 2D cine radial MR and semi-automated analysis using standard clinical software, as compared to the NUFFT k-t ESPIRiT approach.

Diffusion-magnetic resonance imaging predicts decline of kidney function in chronic kidney disease and in patients with a kidney allograft.

Kidney cortical interstitial fibrosis is highly predictive of kidney prognosis and is currently assessed by evaluation of a biopsy. Diffusion-weighted magnetic resonance imaging is a promising non-invasive tool to evaluate kidney fibrosis. We recently adapted diffusion-weighted imaging sequence for discrimination between the kidney cortex and medulla and found that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) correlated with histological interstitial fibrosis. Here, we assessed whether ΔADC as measured with diffusion-weighted magnetic resonance imaging is predictive of kidney function decline and dialysis initiation in chronic kidney disease (CKD) and patients with a kidney allograft in a prospective study encompassing 197 patients. We measured ΔADC in 43 patients with CKD (estimated GFR (eGFR) 55ml/min/1.73m2) and 154 patients with a kidney allograft (eGFR 53ml/min/1.73m2). Patients underwent a kidney biopsy and diffusion-weighted magnetic resonance imaging within one week of biopsy; median follow-up of 2.2 years with measured laboratory parameters. The primary outcome was a rapid decline of kidney function (eGFR decline over 30% or dialysis initiation) during follow up. Significantly, patients with a negative ΔADC had 5.4 times more risk of rapid decline of kidney function or dialysis (95% confidence interval: 2.29-12.58). After correction for kidney function at baseline and proteinuria, low ADC still predicted significant kidney function loss with a hazard ratio of 4.62 (95% confidence interval 1.56-13.67) independent of baseline age, sex, eGFR and proteinuria. Thus, low ΔADC can be a predictor of kidney function decline and dialysis initiation in patients with native kidney disease or kidney allograft, independent of baseline kidney function and proteinuria.

Physiologically variable ventilation reduces regional lung inflammation in a pediatric model of acute respiratory distress syndrome.

BACKGROUND: Benefits of variable mechanical ventilation based on the physiological breathing pattern have been observed both in healthy and injured lungs. These benefits have not been characterized in pediatric models and the effect of this ventilation mode on regional distribution of lung inflammation also remains controversial. Here, we compare structural, molecular and functional outcomes reflecting regional inflammation between PVV and conventional pressure-controlled ventilation (PCV) in a pediatric model of healthy lungs and acute respiratory distress syndrome (ARDS). METHODS: New-Zealand White rabbit pups (n = 36, 670 ± 20 g [half-width 95% confidence interval]), with healthy lungs or after induction of ARDS, were randomized to five hours of mechanical ventilation with PCV or PVV. Regional lung aeration, inflammation and perfusion were assessed using x-ray computed tomography, positron-emission tomography and single-photon emission computed tomography, respectively. Ventilation parameters, blood gases and respiratory tissue elastance were recorded hourly. RESULTS: Mechanical ventilation worsened respiratory elastance in healthy and ARDS animals ventilated with PCV (11 ± 8%, 6 ± 3%, p < 0.04), however, this trend was improved by PVV (1 ± 4%, - 6 ± 2%). Animals receiving PVV presented reduced inflammation as assessed by lung normalized [18F]fluorodeoxyglucose uptake in healthy (1.49 ± 0.62 standardized uptake value, SUV) and ARDS animals (1.86 ± 0.47 SUV) compared to PCV (2.33 ± 0.775 and 2.28 ± 0.3 SUV, respectively, p < 0.05), particularly in the well and poorly aerated lung zones. No benefit of PVV could be detected on regional blood perfusion or blood gas parameters. CONCLUSIONS: Variable ventilation based on a physiological respiratory pattern, compared to conventional pressure-controlled ventilation, reduced global and regional inflammation in both healthy and injured lungs of juvenile rabbits.

Benefit of Physiologically Variable Over Pressure-Controlled Ventilation in a Model of Chronic Obstructive Pulmonary Disease: A Randomized Study.

INTRODUCTION: The advantages of physiologically variable ventilation (PVV) based on a spontaneous breathing pattern have been demonstrated in several respiratory conditions. However, its potential benefits in chronic obstructive pulmonary disease (COPD) have not yet been characterized. We used an experimental model of COPD to compare respiratory function outcomes after 6 h of PVV versus conventional pressure-controlled ventilation (PCV). MATERIALS AND METHODS: Rabbits received nebulized elastase and lipopolysaccharide throughout 4 weeks. After 30 days, animals were anesthetized, tracheotomized, and randomized to receive 6 h of physiologically variable (n = 8) or conventional PCV (n = 7). Blood gases, respiratory mechanics, and chest fluoroscopy were assessed hourly. RESULTS: After 6 h of ventilation, animals receiving variable ventilation demonstrated significantly higher oxygenation index (PaO2/FiO2 441 ± 37 (mean ± standard deviation) versus 354 ± 61 mmHg, p < 0.001) and lower respiratory elastance (359 ± 36 versus 463 ± 81 cmH2O/L, p < 0.01) than animals receiving PCV. Animals ventilated with the variable mode also presented less lung derecruitment (decrease in lung aerated area, -3.4 ± 9.9 versus -17.9 ± 6.7%, p < 0.01) and intrapulmonary shunt fraction (9.6 ± 4.1 versus 17.0 ± 5.8%, p < 0.01). CONCLUSION: PVV applied to a model of COPD improved oxygenation, respiratory mechanics, lung aeration, and intrapulmonary shunt fraction compared to conventional ventilation. A reduction in alveolar derecruitment and lung tissue stress leading to better aeration and gas exchange may explain the benefits of PVV.

Oncogene and tumor suppressor gene expression changes in the peripheral blood leukocytes of patients with colorectal cancer.

AIMS AND BACKGROUND: The mortality of colorectal cancer continues to stagnate despite the development of new therapeutic approaches. Therefore, identifying high-risk population groups could contribute to the prevention of a considerable part of deaths caused by colorectal tumors. METHODS: Fifty patients with colon cancer and 50 patients with other, nonmalignant diseases were selected for the study. Expression of the c-myc, Ha-ras and p53 genes was determined in the peripheral leukocytes of the participants. RESULTS: Marked elevations of the expression of all three investigated genes were seen in the colon cancer patients when compared to the controls. CONCLUSIONS: Our investigations showed that increases in the expression of c-myc, Ha-ras and p53 genes can be demonstrated in the peripheral leukocytes of colon cancer patients. By applying our method to clinical investigations, individuals with a high risk of having developed colon cancer may be identified and early diagnosis may be established.

[The results of Lichtenstein operation for groin hernias--prospective multicenter study]. / Lágyéksérvek Lichtenstein mutéttel történo megoldásának eredményei. Prospektív multicentrikus tanulmány.

UNLABELLED: Authors describe the short and long term results of a prospective multicentric Lichtenstein-trial started in March 1999. For the first time in our country, the exchange of information between the participating institutes has been arranged via Internet. 1434 patients were admitted for primary hernia repair and included in the trial. However, only 714 (49.8 per cent) have attended at the last follow-up control 4 years after surgery. Premilene and Prolene meshes were used in the course of Lichtenstein's tension-free procedure. RESULTS: Wound suppuration occurred only in a very small number of the patients (0.76 per cent) and there was merely one occasion when the mesh implant had to be removed because of sepsis. The intensity of postoperative pain and demand for analgesics was very low. During the follow-up period of 4 years 16 recurrent hernias were diagnosed (2.4 per cent). A hydrocele developed in 8 patients (0.5 per cent) while necrosis of the testicle was found in 4 patients (0.27 per cent). We realised that both the attitude and practice of the institutes participating in the study has changed thoroughly and the Bassini-repair seems to be replaced by the Lichtenstein procedure in these surgical departments. CONCLUSION: The study has reached its objective in more aspects: First it helped to achieve a significant reduction in recurrence rates and it also has shown that there is no increase in wound suppuration. The great number of surgeons performing this kind of inguinal hernia repair and their good results also indicate that this operation in less depending on surgical skills and practice than the Bassini-repair. The study has largely contributed to the national spread of this operation and has doubtlessly verified the advantage of information and data processing through the Internet, ie. a prompt and correct evaluation of the data recorded

Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.

Gastrointestinal stromal tumours in a single institute: is there an association to other gastrointestinal malignancies?

Our knowledge of Gastrointestinal Stromal Tumours (GIST) has been broadened in the last few years by the discovery of the key function of c-kit tyrosine kinase mutation in their pathogenesis. A single institution database is presented and a hypothesis is examined regarding probable connection between GIST and other gastrointestinal malignancies. Between 2000 and 2004 20 patients were admitted to our department with GIS tumour. With the addition of three cases detected between 1991 and 2000, and proved to be GIST retrospectively, 23 cases are followed. Mean age was 64.52 years, male to female ratio 11:12. Ten tumours originated from the stomach, ten from small bowel, one from rectum and two from mesenterium. All patients underwent surgery, 16 operations were completed with R0 radicality, one R1 and four R2 resections were performed. Follow-up ranged from 1 to 157 months. Five out of 23 patients died (21.7%), six patients live with metastatic disease, twelve are disease free. Amongst patient-, tumour- and treatment-related factors the prognostic significance of Fletcher's risk and radicality of resection was demonstrated (p<0.05). Significantly more synchronous or metachronous gastrointestinal malignancies were found is this population of GIST patients, when compared to the prevalence of malignancies in normal Hungarian population (p<0.001).

[Results of 300 kidney transplantations]. / 300 vesetranszplantáció eredményei.

Kidney transplantation is a widely used method for the treatment o fend-stage renal disease. Between September 3, 1993 and December 2002 a total of 300 kidney transplantations were performed at the Department of Surgery at the Medical University of Pécs. In 24 patients simultaneous kidney and pancreas transplantation was performed. The mean age of the 189 male and 111 female patients was 42 years. The HLA B, Dr tissue antigen mismatches was 1.63. The average cold ischemic time was 1199 minutes whereas the average anastomotic time was 43 minutes. Early surgical complications happened to 16 patients. In spite of the immunosuppressive treatment 26 acute steroid resistant rejection have occurred, 9 of which were irreversible. In our opinion the meticulous surgical technique is as important as the postoperative care is. The early and late complications of 300 renal transplants are reviewed by the authors.