Alignment of contrast enhanced medical images

The re-alignment of series of medical images in which there are multiple contrast variations is difficult. The reason for this is that the popularmeasures of image similarity used to drive the alignment procedure do not separate the influence of intensity variation due to image feature motion and intensity variation due to feature enhancement. In particular, the appearance of new structure poses problems when it has no representation in the original image. The acquisition of many images over time, such as in dynamic contrast enhanced MRI, requires that many images with different contrast be registered to the same coordinate system, compounding the problem. This thesis addresses these issues, beginning by presenting conditions under which conventional registration fails and proposing a solution in the form of a ’progressive principal component registration’. The algorithm uses a statistical analysis of a series of contrast varying images in order to reduce the influence of contrast-enhancement that would otherwise distort the calculation of the image similarity measures used in image registration. The algorithm is shown to be versatile in that it may be applied to series of images in which contrast variation is due to either temporal contrast enhancement changes, as in dynamic contrast-enhanced MRI or intrinsically in the image selection procedure as in diffusion weighted MRI

Performance of a fully automatic lesion detection system for breast DCE-MRI

PURPOSE: To describe and test a new fully automatic lesion detection system for breast DCE-MRI. MATERIALS AND METHODS: Studies were collected from two institutions adopting different DCE-MRI sequences, one with and the other one without fat-saturation. The detection pipeline consists of (i) breast segmentation, to identify breast size and location; (ii) registration, to correct for patient movements; (iii) lesion detection, to extract contrast-enhanced regions using a new normalization technique based on the contrast-uptake of mammary vessels; (iv) false positive (FP) reduction, to exclude contrast-enhanced regions other than lesions. Detection rate (number of system-detected malignant and benign lesions over the total number of lesions) and sensitivity (system-detected malignant lesions over the total number of malignant lesions) were assessed. The number of FPs was also assessed. RESULTS: Forty-eight studies with 12 benign and 53 malignant lesions were evaluated. Median lesion diameter was 6 mm (range, 5-15 mm) for benign and 26 mm (range, 5-75 mm) for malignant lesions. Detection rate was 58/65 (89%; 95% confidence interval [CI] 79%-95%) and sensitivity was 52/53 (98%; 95% CI 90%-99%). Mammary median FPs per breast was 4 (1st-3rd quartiles 3-7.25). CONCLUSION: The system showed promising results on MR datasets obtained from different scanners producing fat-sat or non-fat-sat images with variable temporal and spatial resolution and could potentially be used for early diagnosis and staging of breast cancer to reduce reading time and to improve lesion detection. Further evaluation is needed before it may be used in clinical practice

4D Non-rigid registration of renal dynamic contrast enhanced MRI data

Master'sMASTER OF ENGINEERIN

3D fusion of histology to multi-parametric MRI for prostate cancer imaging evaluation and lesion-targeted treatment planning

Multi-parametric magnetic resonance imaging (mpMRI) of localized prostate cancer has the potential to support detection, staging and localization of tumors, as well as selection, delivery and monitoring of treatments. Delineating prostate cancer tumors on imaging could potentially further support the clinical workflow by enabling precise monitoring of tumor burden in active-surveillance patients, optimized targeting of image-guided biopsies, and targeted delivery of treatments to decrease morbidity and improve outcomes. Evaluating the performance of mpMRI for prostate cancer imaging and delineation ideally includes comparison to an accurately registered reference standard, such as prostatectomy histology, for the locations of tumor boundaries on mpMRI. There are key gaps in knowledge regarding how to accurately register histological reference standards to imaging, and consequently further gaps in knowledge regarding the suitability of mpMRI for tasks, such as tumor delineation, that require such reference standards for evaluation. To obtain an understanding of the magnitude of the mpMRI-histology registration problem, we quantified the position, orientation and deformation of whole-mount histology sections relative to the formalin-fixed tissue slices from which they were cut. We found that (1) modeling isotropic scaling accounted for the majority of the deformation with a further small but statistically significant improvement from modeling affine transformation, and (2) due to the depth (mean±standard deviation (SD) 1.1±0.4 mm) and orientation (mean±SD 1.5±0.9°) of the sectioning, the assumption that histology sections are cut from the front faces of tissue slices, common in previous approaches, introduced a mean error of 0.7 mm. To determine the potential consequences of seemingly small registration errors such as described above, we investigated the impact of registration accuracy on the statistical power of imaging validation studies using a co-registered spatial reference standard (e.g. histology images) by deriving novel statistical power formulae that incorporate registration error. We illustrated, through a case study modeled on a prostate cancer imaging trial at our centre, that submillimeter differences in registration error can have a substantial impact on the required sample sizes (and therefore also the study cost) for studies aiming to detect mpMRI signal differences due to 0.5 – 2.0 cm3 prostate tumors. With the aim of achieving highly accurate mpMRI-histology registrations without disrupting the clinical pathology workflow, we developed a three-stage method for accurately registering 2D whole-mount histology images to pre-prostatectomy mpMRI that allowed flexible placement of cuts during slicing for pathology and avoided the assumption that histology sections are cut from the front faces of tissue slices. The method comprised a 3D reconstruction of histology images, followed by 3D–3D ex vivo–in vivo and in vivo–in vivo image transformations. The 3D reconstruction method minimized fiducial registration error between cross-sections of non-disruptive histology- and ex-vivo-MRI-visible strand-shaped fiducials to reconstruct histology images into the coordinate system of an ex vivo MR image. We quantified the mean±standard deviation target registration error of the reconstruction to be 0.7±0.4 mm, based on the post-reconstruction misalignment of intrinsic landmark pairs. We also compared our fiducial-based reconstruction to an alternative reconstruction based on mutual-information-based registration, an established method for multi-modality registration. We found that the mean target registration error for the fiducial-based method (0.7 mm) was lower than that for the mutual-information-based method (1.2 mm), and that the mutual-information-based method was less robust to initialization error due to multiple sources of error, including the optimizer and the mutual information similarity metric. The second stage of the histology–mpMRI registration used interactively defined 3D–3D deformable thin-plate-spline transformations to align ex vivo to in vivo MR images to compensate for deformation due to endorectal MR coil positioning, surgical resection and formalin fixation. The third stage used interactively defined 3D–3D rigid or thin-plate-spline transformations to co-register in vivo mpMRI images to compensate for patient motion and image distortion. The combined mean registration error of the histology–mpMRI registration was quantified to be 2 mm using manually identified intrinsic landmark pairs. Our data set, comprising mpMRI, target volumes contoured by four observers and co-registered contoured and graded histology images, was used to quantify the positive predictive values and variability of observer scoring of lesions following the Prostate Imaging Reporting and Data System (PI-RADS) guidelines, the variability of target volume contouring, and appropriate expansion margins from target volumes to achieve coverage of histologically defined cancer. The analysis of lesion scoring showed that a PI-RADS overall cancer likelihood of 5, denoting “highly likely cancer”, had a positive predictive value of 85% for Gleason 7 cancer (and 93% for lesions with volumes \u3e0.5 cm3 measured on mpMRI) and that PI-RADS scores were positively correlated with histological grade (ρ=0.6). However, the analysis also showed interobserver differences in PI-RADS score of 0.6 to 1.2 (on a 5-point scale) and an agreement kappa value of only 0.30. The analysis of target volume contouring showed that target volume contours with suitable margins can achieve near-complete histological coverage for detected lesions, despite the presence of high interobserver spatial variability in target volumes. Prostate cancer imaging and delineation have the potential to support multiple stages in the management of localized prostate cancer. Targeted biopsy procedures with optimized targeting based on tumor delineation may help distinguish patients who need treatment from those who need active surveillance. Ongoing monitoring of tumor burden based on delineation in patients undergoing active surveillance may help identify those who need to progress to therapy early while the cancer is still curable. Preferentially targeting therapies at delineated target volumes may lower the morbidity associated with aggressive cancer treatment and improve outcomes in low-intermediate-risk patients. Measurements of the accuracy and variability of lesion scoring and target volume contouring on mpMRI will clarify its value in supporting these roles

MR to Ultrasound Registration for Image-Guided Prostate Biopsy

Transrectal ultrasound (TRUS) guided prostate biopsy is the standard approach for diagnosis of prostate cancer (PCa). However, due to the lack of image contrast of prostate tumors, it often results in false negatives. Magnetic Resonance Imaging (MRI) has been considered to be a promising imaging modality for noninvasive identification of PCa, since it can provide a high sensitivity and specificity for the detection of early stage PCa. Our main objective is to develop a registration method of 3D MR-TRUS images, allowing generation of volumetric 3D maps of targets identified in 3D MR images to be biopsied using 3D TRUS images. We proposed an image-based non-rigid registration approach which employs the modality independent neighborhood descriptor (MIND) as the local similarity feature. An efficient duality-based convex optimization-based algorithmic scheme was introduced to extract the deformations. The registration accuracy was evaluated using 20 patient images by calculating the target registration error (TRE) using manually identified corresponding intrinsic fiducials. Additional performance metrics (DSC, MAD, and MAXD) were also calculated by comparing the MR and TRUS manually segmented prostate surfaces in the registered images. Experimental results showed that the proposed method yielded an overall median TRE of 1.76 mm. In addition, we proposed a surface-based registration method, which first makes use of an initial rigid registration of 3D MR to TRUS using 6 manually placed corresponding landmarks in each image. Following the manual initialization, two prostate surfaces are segmented from 3D MR and TRUS images and then non-rigidly registered using a thin-plate spline algorithm. The registration accuracy was evaluated using 17 patient images by measuring TRE. Experimental results show that the proposed method yielded an overall mean TRE of 2.24 mm, which is favorably comparable to a clinical requirement for an error of less than 2.5 mm

Real-time Prostate Motion Tracking For Robot-assisted Laparoscopic Radical Prostatectomy

Radical prostatectomy surgery (RP) is the gold standard for treatment of localized prostate cancer (PCa). Recently, emergence of minimally invasive techniques such as Laparoscopic Radical Prostatectomy (LRP) and Robot-Assisted Laparoscopic Radical Prostatectomy (RARP) has improved the outcomes for prostatectomy. However, it remains difficult for surgeons to make informed decisions regarding resection margins and nerve sparing since the location of the tumour within the organ is not usually visible in a laparoscopic view. While MRI enables visualization of the salient structures and cancer foci, its efficacy in LRP is reduced unless it is fused into a stereoscopic view such that homologous structures overlap. Registration of the MRI image and peri-operative ultrasound image either via visual manual alignment or using a fully automated registration can potentially be exploited to bring the pre-operative information into alignment with the patient coordinate system at the beginning of the procedure. While doing so, prostate motion needs to be compensated in real-time to synchronize the stereoscopic view with the pre-operative MRI during the prostatectomy procedure. In this thesis, two tracking methods are proposed to assess prostate rigid rotation and translation for the prostatectomy. The first method presents a 2D-to-3D point-to-line registration algorithm to measure prostate motion and translation with respect to an initial 3D TRUS image. The second method investigates a point-based stereoscopic tracking technique to compensate for rigid prostate motion so that the same motion can be applied to the pre-operative images

Quantification of tumour heterogenity in MRI

Cancer is the leading cause of death that touches us all, either directly or indirectly. It is estimated that the number of newly diagnosed cases in the Netherlands will increase to 123,000 by the year 2020. General Dutch statistics are similar to those in the UK, i.e. over the last ten years, the age-standardised incidence rate1 has stabilised at around 355 females and 415 males per 100,000. Figure 1 shows the cancer incidence per gender. In the UK, the rise in lifetime risk of cancer is more than one in three and depends on many factors, including age, lifestyle and genetic makeup

Model-driven registration for multi-parametric renal MRI

The use of MR imaging biomarkers is a promising technique that may assist towards faster prognosis and more accurate diagnosis of diseases like diabetic kidney disease (DKD). The quantification of MR Imaging renal biomarkers from multiparametric MRI is a process that requires a physiological model to be fitted on the data. This process can provide accurate estimates only under the assumption that there is pixelto-pixel correspondence between images acquired over different time points. However, this is rarely the case due to motion artifacts (breathing, involuntary muscle relaxation) introduced during the acquisition. Hence, it is of vital importance for a biomarkers quantification pipeline to include a motion correctionstep in order to properly align the images and enable a more accurate parameter estimation. This study aims in testing whether a Model Driven Registration (MDR), which integrates physiological models in the registration process itself, can serve as a universal solution for the registration of multiparametric renal MRI. MDR is compared with a state-of-the-art model-free motion correction approach for multiparametric MRI, that minimizes a Principal Components Analysis based metric, performing a groupwise registration. The results of the two methods are compared on T1, DTI and DCE-MRI data for a small cohort of 10 DKD patients, obtained from BEAt-DKD project’s digital database. The majority of the evaluation metrics used to compare the two methods indicated that MDR achieved better registration results, while requiring significantly lower computational times. In conclusion, MDR could be considered as the method of choice for motion correction of multiparametric quantitative renal MRI

Computer-Aided Detection and diagnosis for prostate cancer based on mono and multi-parametric MRI: A review

International audienceProstate cancer is the second most diagnosed cancer of men all over the world. In the last decades, new imaging techniques based on Magnetic Resonance Imaging (MRI) have been developed improving diagnosis.In practise, diagnosis can be affected by multiple factors such as observer variability and visibility and complexity of the lesions. In this regard, computer-aided detection and computer-aided diagnosis systemshave been designed to help radiologists in their clinical practice. Research on computer-aided systems specifically focused for prostate cancer is a young technology and has been part of a dynamic field ofresearch for the last ten years. This survey aims to provide a comprehensive review of the state of the art in this lapse of time, focusing on the different stages composing the work-flow of a computer-aidedsystem. We also provide a comparison between studies and a discussion about the potential avenues for future research. In addition, this paper presents a new public online dataset which is made available to theresearch community with the aim of providing a common evaluation framework to overcome some of the current limitations identified in this survey

GIFTed Demons: deformable image registration with local structure-preserving regularization using supervoxels for liver applications.

Deformable image registration, a key component of motion correction in medical imaging, needs to be efficient and provides plausible spatial transformations that reliably approximate biological aspects of complex human organ motion. Standard approaches, such as Demons registration, mostly use Gaussian regularization for organ motion, which, though computationally efficient, rule out their application to intrinsically more complex organ motions, such as sliding interfaces. We propose regularization of motion based on supervoxels, which provides an integrated discontinuity preserving prior for motions, such as sliding. More precisely, we replace Gaussian smoothing by fast, structure-preserving, guided filtering to provide efficient, locally adaptive regularization of the estimated displacement field. We illustrate the approach by applying it to estimate sliding motions at lung and liver interfaces on challenging four-dimensional computed tomography (CT) and dynamic contrast-enhanced magnetic resonance imaging datasets. The results show that guided filter-based regularization improves the accuracy of lung and liver motion correction as compared to Gaussian smoothing. Furthermore, our framework achieves state-of-the-art results on a publicly available CT liver dataset