Martin O. Leach

Nonrigid registration using free-form deformations: application to breast MR images

In this paper the authors present a new approach for the nonrigid registration of contrast-enhanced breast MRI. A hierarchical transformation model of the motion of the breast has been developed. The global motion of the breast is modeled by an affine transformation while the local breast motion is described by a free-form deformation (FFD) based on B-splines. Normalized mutual information is used as a voxel-based similarity measure which is insensitive to intensity changes as a result of the contrast enhancement. Registration is achieved by minimizing a cost function, which represents a combination of the cost associated with the smoothness of the transformation and the cost associated with the image similarity. The algorithm has been applied to the fully automated registration of three-dimensional (3-D) breast MRI in volunteers and patients. In particular, the authors have compared the results of the proposed nonrigid registration algorithm to those obtained using rigid and affine registration techniques. The results clearly indicate that the nonrigid registration algorithm is much better able to recover the motion and deformation of the breast than rigid or affine registration algorithms.

American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.

New evidence on breast Magnetic Resonance Imaging (MRI) screening has become available since the American Cancer Society (ACS) last issued guidelines for the early detection of breast cancer in 2003. A guideline panel has reviewed this evidence and developed new recommendations for women at different defined levels of risk. Screening MRI is recommended for women with an approximately 20–25% or greater lifetime risk of breast cancer, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin disease. There are several risk subgroups for which the available data are insufficient to recommend for or against screening, including women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography. Diagnostic uses of MRI were not considered to be within the scope of this review.

Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS)

BACKGROUND Women genetically predisposed to breast cancer often develop the disease at a young age when dense breast tissue reduces the sensitivity of X-ray mammography. Our aim was, therefore, to compare contrast enhanced magnetic resonance imaging (CE MRI) with mammography for screening. METHODS We did a prospective multicentre cohort study in 649 women aged 35-49 years with a strong family history of breast cancer or a high probability of a BRCA1, BRCA2, or TP53 mutation. We recruited participants from 22 centres in the UK, and offered the women annual screening with CE MRI and mammography for 2-7 years. FINDINGS We diagnosed 35 cancers in the 649 women screened with both mammography and CE MRI (1881 screens): 19 by CE MRI only, six by mammography only, and eight by both, with two interval cases. Sensitivity was significantly higher for CE MRI (77%, 95% CI 60-90) than for mammography (40%, 24-58; p=0.01), and was 94% (81-99) when both methods were used. Specificity was 93% (92-95) for mammography, 81% (80-83) for CE MRI (p<0.0001), and 77% (75-79) with both methods. The difference between CE MRI and mammography sensitivities was particularly pronounced in BRCA1 carriers (13 cancers; 92%vs 23%, p=0.004). INTERPRETATION Our findings indicate that CE MRI is more sensitive than mammography for cancer detection. Specificity for both procedures was acceptable. Despite a high proportion of grade 3 cancers, tumours were small and few women were node positive. Annual screening, combining CE MRI and mammography, would detect most tumours in this risk group.

The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations

Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.

Predicting Response of Colorectal Hepatic Metastasis: Value of Pretreatment Apparent Diffusion Coefficients

OBJECTIVE The purposes of this study were to determine whether the pretreatment apparent diffusion coefficients (ADCs) of hepatic metastatic lesions from colorectal cancer are predictive of response to chemotherapy and to compare the ADCs of metastatic lesions before and after chemotherapy. SUBJECTS AND METHODS Twenty patients with potentially operable hepatic lesions larger than 1 cm in diameter metastatic from colorectal carcinoma were prospectively evaluated with diffusion-weighted imaging at three b values before and after chemotherapy. Quantitative ADC maps were calculated with images with b values of 0, 150, and 500 s/mm2 (ADC0-500) and with images with b values of 150 and 500 s/mm2 (ADC150-500). Regions of interest were drawn around metastatic lesions and randomly over liver. The mean ADC0-500 and mean ADC150-500 of metastatic lesions before and after chemotherapy were compared according to response defined by Response Evaluation Criteria in Solid Tumors criteria. RESULTS Twenty-five responding and 15 nonresponding metastatic lesions were evaluated. Nonresponding lesions had a significantly higher pretreatment mean ADC0-500 and mean ADC150-500 than did responding lesions (Mann-Whitney U test, p < 0.002). There was a linear regression relation (r2 = 0.34, p = 0.02) between percentage size reduction of metastatic lesions and pretreatment mean ADC150-500. After chemotherapy, responding lesions had a significant increase in mean ADC0-500 and ADC150-500 (Wilcoxons signed rank, p = 0.025). No significant change was observed in nonresponding metastatic lesions (Wilcoxons signed rank, p > 0.5) or in normal liver parenchyma (Wilcoxons signed rank, p > 0.4). CONCLUSION High pretreatment mean ADC0-500 and mean ADC150-500 of colorectal hepatic metastatic lesions were predictive of poor response to chemotherapy. A significant increase in mean ADC0-500 and ADC150-500 was observed in metastatic lesions that responded to chemotherapy. These findings may have implications for development of individualized therapy.

Validation of nonrigid image registration using finite-element methods: application to breast MR images

Presents a novel method for validation of nonrigid medical image registration. This method is based on the simulation of physically plausible, biomechanical tissue deformations using finite-element methods. Applying a range of displacements to finite-element models of different patient anatomies generates model solutions which simulate gold standard deformations. From these solutions, deformed images are generated with a range of deformations typical of those likely to occur in vivo. The registration accuracy with respect to the finite-element simulations is quantified by co-registering the deformed images with the original images and comparing the recovered voxel displacements with the biomechanically simulated ones. The functionality of the validation method is demonstrated for a previously described nonrigid image registration technique based on free-form deformations using B-splines and normalized mutual information as a voxel similarity measure, with an application to contrast-enhanced magnetic resonance mammography image pairs. The exemplar nonrigid registration technique is shown to be of subvoxel accuracy on average for this particular application. The validation method presented here is an important step toward more generic simulations of biomechanically plausible tissue deformations and quantification of tissue motion recovery using nonrigid image registration. It will provide a basis for improving and comparing different nonrigid registration techniques for a diversity of medical applications, such as intrasubject tissue deformation or motion correction in the brain, liver or heart.

Evaluating the effect of rectal distension and rectal movement on prostate gland position using cine MRI

PURPOSE To evaluate the dynamic interrelationship between rectal distension and rectal movements, and to determine the effect of rectal movement on the position of the prostatic gland using cine magnetic resonance imaging (MRI). METHODS AND MATERIALS Fifty-five patients with biopsy-proven or suspected prostate cancer were examined in the axial plane using repeated spoiled gradient-echo sequences every 10 seconds for 7 minutes. Twenty-four patients received bowel relaxants before imaging. Images were analyzed for the degree of rectal distension, for the incidence, magnitude, and number of rectal and prostate movements. RESULTS Rectal movements were seen in 28 (51%) patients overall, in 10 (42%) of those receiving bowel relaxants and in 18 (58%) not receiving bowel relaxants. The incidence of rectal movements correlated with the degree of rectal distension (p = 0.0005), but the magnitude of rectal movements did not correlate with the degree of rectal distension. Eighty-six rectal movements resulting in 33 anterior-posterior (AP) prostate movements were seen. The magnitude of rectal movements correlated well with degree of prostate movements (p < 0.001). Prostate movements in the AP direction were seen in 16 (29%) patients, and in 9 (16%) patients the movement was greater than 5 mm. The median prostate AP displacement was anterior by 4.2 (-5 to +14 mm). CONCLUSIONS Cine MRI is able to demonstrate near real time rectal and associated prostate movements. Rectal movements are related to rectal distension and result in significant displacements of the prostate gland over a time period similar to that used for daily fractionated radiotherapy treatments. Delivery of radiotherapy needs to take into account these organ movements.

Magnetic resonance imaging (MRI): considerations and applications in radiotherapy treatment planning.

The emerging utilisation of conformal radiotherapy (RT) planning requires sophisticated imaging modalities. Magnetic resonance imaging (MRI) has introduced several added imaging benefits that may confer an advantage over the use of computed tomography (CT) in RT planning such as improved soft tissue definition, unrestricted multiplannar and volumetric imaging as well as physiological and biochemical information with magnetic resonance (MR) angiography and spectroscopy. However, MRI has not yet seriously challenged CT for RT planning in most sites. The reasons for this include: (1) the poor imaging of bone and the lack of electron density information from MRI required for dosimetry calculations; (2) the presence of intrinsic system-related and object-induced MR image distortions; (3) the paucity of widely available computer software to accurately and reliably integrate and manipulate MR images within existing RT planning systems. In this review, the basic principals of MRI with its present potential and limitations for RT planning as well as possible solutions will be examined. Methods of MRI data acquisition and processing including image segmentation and registration to allow its application in RT planning will be discussed. Despite the difficulties listed, MRI has complemented CT-based RT planning and in some regions of the body especially the brain, it has been used alone with some success. Recent work with doped gel compounds allow the MRI mapping of dose distributions thus potentially providing a quality assurance tool and in a manner analogous to CT, the production of dose-response information in the form of dose volume histograms. However, despite the promise of MRI, much development research remains before its full potential and cost-effectiveness can be assessed.

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

IntroductionBreast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.MethodsMore than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.ResultsThe 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working.ConclusionsWith resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.