Development of a registration framework to validate MRI with histology for prostate focal therapy.

PURPOSE: Focal therapy has been proposed as an alternative method to whole-gland treatment for prostate cancer when aiming to reduce treatment side effects. The authors recently validated a radiobiological model which takes into account tumor location and tumor characteristics including tumor cell density, Gleason score, and hypoxia in order to plan optimal dose distributions for focal therapy. The authors propose that this model can be informed using multiparametric MRI (mpMRI) and in this study present a registration framework developed to map prostate mpMRI and histology data, where histology will provide the "ground truth" data regarding tumor location and biology. The authors aim to apply this framework to a growing database to develop a prostate biological atlas which will enable MRI based planning for prostate focal therapy treatment. METHODS: Six patients scheduled for routine radical prostatectomy were used in this proof-of-concept study. Each patient underwent mpMRI scanning prior to surgery, after which the excised prostate specimen was formalin fixed and mounted in agarose gel in a custom designed sectioning box. T2-weighted MRI of the specimen in the sectioning box was acquired, after which 5 mm sections of the prostate were cut and histology sections were microtomed. A number of image processing and registration steps were used to register histology images with ex vivo MRI and deformable image registration (DIR) was applied to 3D T2w images to align the in vivo and ex vivo MRI data. Dice coefficient metrics and corresponding feature points from two independent annotators were selected in order to assess the DIR accuracy. RESULTS: Images from all six patients were registered, providing histology and in vivo MRI in the ex vivo MRI frame of reference for each patient. Results demonstrated that their DIR methodology to register in vivo and ex vivo 3D T2w MRI improved accuracy in comparison with an initial manual alignment for prostates containing features which were readily visible on MRI. The average estimated uncertainty between in vivo MRI and histology was 3.3 mm, which included an average error of 3.1 mm between in vivo and ex vivo MRI after applying DIR. The mean dice coefficient for the prostate contour between in vivo and ex vivo MRI increased from 0.83 before DIR to 0.93 after DIR. CONCLUSIONS: The authors have developed a registration framework for mapping in vivo MRI data of the prostate with histology by implementing a number of processing steps and ex vivo MRI of the prostate specimen. Validation of DIR was challenging, particularly in prostates with few or mostly linear rather than spherical shaped features. Refinement of their MR imaging protocols to improve the data quality is currently underway which may improve registration accuracy. Additional mpMRI sequences will be registered within this framework to quantify prostate tumor location and biology.

Improving Multiple Sclerosis Plaque Detection Using a Semiautomated Assistive Approach.

BACKGROUND AND PURPOSE: Treating MS with disease-modifying drugs relies on accurate MR imaging follow-up to determine the treatment effect. We aimed to develop and validate a semiautomated software platform to facilitate detection of new lesions and improved lesions. MATERIALS AND METHODS: We developed VisTarsier to assist manual comparison of volumetric FLAIR sequences by using interstudy registration, resectioning, and color-map overlays that highlight new lesions and improved lesions. Using the software, 2 neuroradiologists retrospectively assessed MR imaging MS comparison study pairs acquired between 2009 and 2011 (161 comparison study pairs met the study inclusion criteria). Lesion detection and reading times were recorded. We tested inter- and intraobserver agreement and comparison with original clinical reports. Feedback was obtained from referring neurologists to assess the potential clinical impact. RESULTS: More comparison study pairs with new lesions (reader 1, n = 60; reader 2, n = 62) and improved lesions (reader 1, n = 28; reader 2, n = 39) were recorded by using the software compared with original radiology reports (new lesions, n = 20; improved lesions, n = 5); the difference reached statistical significance (P < .001). Interobserver lesion number agreement was substantial (≥1 new lesion: κ = 0.87; 95% CI, 0.79-0.95; ≥1 improved lesion: κ = 0.72; 95% CI, 0.59-0.85), and overall interobserver lesion number correlation was good (Spearman ρ: new lesion = 0.910, improved lesion = 0.774). Intraobserver agreement was very good (new lesion: κ = 1.0, improved lesion: κ = 0.94; 95% CI, 0.82-1.00). Mean reporting times were <3 minutes. Neurologists indicated retrospective management alterations in 79% of comparative study pairs with newly detected lesion changes. CONCLUSIONS: Using software that highlights changes between study pairs can improve lesion detection. Neurologist feedback indicated a likely impact on management.

Automated and semi-automated cell tracking: addressing portability challenges.

Cell tracking is a key task in the high-throughput quantitative study of important biological processes, such as immune system regulation and neurogenesis. Variability in cell density and dynamics in different videos, hampers portability of existing trackers across videos. We address these potability challenges in order to develop a portable cell tracking algorithm. Our algorithm can handle noise in cell segmentation as well as divisions and deaths of cells. We also propose a parameter-free variation of our tracker. In the tracker, we employ a novel method for recovering the distribution of cell displacements. Further, we present a mathematically justified procedure for determining the gating distance in relation to tracking performance. For the range of real videos tested, our tracker correctly recovers on average 96% of cell moves, and outperforms an advanced probabilistic tracker when the cell detection quality is high. The scalability of our tracker was tested on synthetic videos with up to 200 cells per frame. For more challenging tracking conditions, we propose a novel semi-automated framework that can increase the ratio of correctly recovered tracks by 12%, through selective manual inspection of only 10% of all frames in a video.

Functional aspect of a phosphopeptide derived from calf thymus nuclei and DNA.

Phosphopeptides (PPs) isolated from highly purified calf thymus DNA (N-DNA) and extracted from calf thymus nuclei were fractionated, and the effect of one PP fraction on DNA replication has been examined. In the absence of inhibitors, the increasing PP concentration caused a linear decrease of 3H-thymidine uptake in L5178Y cells. If PP fraction was mildly hydrolysed with 1NHCl, the decrease in uptake was much steeper. The studies in which the inhibitors were used revealed that by the addition of the unhydrolysed PP fraction the inhibition of 3H-thymidine uptake by alpha-amanitin could be completely overcome, and that the inhibition by puromycin was reduced to 65-77% of the control. With puromycin, there was a gradual decrease of 3H-thymidine uptake with PP concentration above 3 mg/ml. The PPs gave an increase in incorporation of 3H-thymidine even after removal of alpha-amanitin and puromycin; thus, it is suggested that there is no direct interaction of either inhibitor with PP in the cell. Data on the utilization of 3H-cytidine for the synthesise of new DNA suggest that PP fraction might cause an acceleration of DNA replication.

Autologous fibrin glue in full-thickness skin grafting.

Full-thickness skin grafts can be anchored to the recipient site using fibrin glue made from the patient's own blood and commercially available thrombin and epsilon aminocaproic acid. The technique works well for small grafts on irregularly contoured sites where suture fixation of a graft would be technically difficult. Full-thickness skin grafts anchored with autologous fibrin glue have been uniformly successful in 50 patients followed for a minimum period of four months.

Necrotizing sialometaplasia of palate.

A patient with necrotizing sialometaplasia of the hard palate was treated with wide resection on a biopsy diagnosis of carcinoma. The literature on this recently identified entity is reviewed and the characteristic clinical features, histopathology and ultrastructure are summarized. To the best of our knowledge, no ultrastructural study concerning this entity has been previously reported. Unless recognized early, an extensive resection might be done needlessly.