Diffusion Is Directional: Innovative Diffusion Tensor Imaging to Improve Prostate Cancer Detection.

In the prostate, water diffusion is faster when moving parallel to duct and gland walls than when moving perpendicular to them, but these data are not currently utilized in multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) detection. Diffusion tensor imaging (DTI) can quantify the directional diffusion of water in tissue and is applied in brain and breast imaging. Our aim was to determine whether DTI may improve PCa detection.

Effect of IV Administration of a Gadolinium-Based Contrast Agent on Breast Diffusion-Tensor Imaging.

The purpose of this study was to quantify changes in diffusion-tensor imaging (DTI) parameters before and after IV administration of a gadolinium-based contrast agent (GBCA) and explore the influence of those parameters on breast cancer diagnosis. A prospective cohort of 26 women with BI-RADS categories 0, 4, 5, or 6 underwent 3-T breast MRI with sequential DTI before GBCA administration and immediately after. Quantitative image analysis using dedicated DTI software yielded parametric DTI maps of each directional diffusion coefficient (DDC), mean diffusivity, and maximal anisotropy of the lesions and normal tissue.

Quantitative evaluation of breast cancer response to neoadjuvant chemotherapy by diffusion tensor imaging: Initial results.

Background: Diffusion tensor imaging (DTI) yields several parameters that have not been tested in response evaluation to neoadjuvant chemotherapy (NAC).

Purpose: To evaluate and compare in reference to histopathology findings the ability of DTI and dynamic contrast-enhanced (DCE) MRI to monitor response to NAC.

Study Type: Retrospective.

Monitoring In-Vivo the Mammary Gland Microstructure during Morphogenesis from Lactation to Post-Weaning Using Diffusion Tensor MRI.

Lactation and the return to the pre-conception state during post-weaning are regulated by hormonal induced processes that modify the microstructure of the mammary gland, leading to changes in the features of the ductal / glandular tissue, the stroma and the fat tissue. These changes create a challenge in the radiological workup of breast disorder during lactation and early post-weaning. Here we present non-invasive MRI protocols designed to record in vivo high spatial resolution, T-weighted images and diffusion tensor images of the entire mammary gland.

Estrogen Receptor-Targeted Contrast Agents for Molecular Magnetic Resonance Imaging of Breast Cancer Hormonal Status.

The estrogen receptor (ER) α is overexpressed in most breast cancers, and its level serves as a major prognostic factor. It is important to develop quantitative molecular imaging methods that specifically detect ER in vivo and assess its function throughout the entire primary breast cancer and in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging (MRI) effects of two novel ER-targeted contrast agents (CAs), based on pyridine-tetra-acetate-Gd(III) chelate conjugated to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd).

Can diffusion tensor anisotropy indices assist in breast cancer detection?

Purpose: To evaluate whether the various anisotropy indices derived from breast diffusion tensor imaging (DTI) can characterize the healthy breast structure and differentiate cancer from normal breast tissue.

Materials And Methods: Six healthy volunteers and retrospectively selected 24 breast cancer patients were imaged at 3T. DTI included two b-values 0 and 700 sec/mm with 20-64 gradient directions and TE of 120 or 90 msec.

Diffusion tensor magnetic resonance imaging of the pancreas.

Purpose: To develop a diffusion-tensor-imaging (DTI) protocol that is sensitive to the complex diffusion and perfusion properties of the healthy and malignant pancreas tissues.

Materials And Methods: Twenty-eight healthy volunteers and nine patients with pancreatic-ductal-adenocacinoma (PDAC), were scanned at 3T with T2-weighted and DTI sequences. Healthy volunteers were also scanned with multi-b diffusion-weighted-imaging (DWI), whereas a standard clinical protocol complemented the PDAC patients' scans.

Tracking the mammary architectural features and detecting breast cancer with magnetic resonance diffusion tensor imaging.

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI).

Overcoming limitations in diffusion-weighted MRI of breast by spatio-temporal encoding.

Purpose: Evaluating the usefulness of diffusion-weighted spatio-temporal encoding (SPEN) methods to provide quantitative apparent diffusion coefficient (ADC)-based characterizations of healthy and malignant human breast tissues, in comparison with results obtained using techniques based on spin-echo echo planar imaging (SE-EPI).

Methods: Twelve healthy volunteers and six breast cancer patients were scanned at 3T using scanner-supplied diffusion-weighted imaging EPI sequences, as well as two fully refocused SPEN variants programmed in-house. Suitable codes were written to process the data, including calculations of the actual b-values and retrieval of the ADC maps.

Diffusion-tensor MR imaging of the breast: hormonal regulation.

Purpose: To investigate the parameters obtained with magnetic resonance (MR) diffusion-tensor imaging (DTI) of the breast throughout the menstrual cycle phases, during lactation, and after menopause, with and without hormone replacement therapy (HRT).

Materials And Methods: All protocols were approved by the internal review board, and signed informed consent was obtained from all participants. Forty-five healthy volunteers underwent imaging by using T2-weighted and DTI MR sequences at 3 T.

In vivo magnetic resonance of hyperpolarized [(13)C1]pyruvate: metabolic dynamics in stimulated muscle.

The metabolic status of muscle changes according to the energetic demands of the organism. Two key regulators of these changes include exercise and insulin, with exercise eliciting catabolic expenditure within seconds and insulin enabling anabolic energy investment over minutes to hours. This study explores the potential of time-resolved hyperpolarized dynamic (13)C spectroscopy to characterize the in vivo metabolic phenotype of muscle during functional and biochemical insulin-induced stimulation of muscle.

Characterization of estrogen-receptor-targeted contrast agents in solution, breast cancer cells, and tumors in vivo.

The estrogen receptor (ER) is a major prognostic biomarker of breast cancer, currently determined in surgical specimens by immunohistochemistry. Two new ER-targeted probes, pyridine-tetra-acetate-Gd chelate (PTA-Gd) conjugated either to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd), were explored as contrast agents for molecular imaging of ER. In solution, both probes exhibited a micromolar ER binding affinity, fast water exchange rate (∼10(7) s(-1)), and water proton-relaxivity of 4.

Parametric diffusion tensor imaging of the breast.

Objectives: To investigate the ability of parametric diffusion tensor imaging (DTI), applied at 3 Tesla, to dissect breast tissue architecture and evaluate breast lesions.

Materials And Methods: All protocols were approved and a signed informed consent was obtained from all subjects. The study included 21 healthy women, 26 women with 33 malignant lesions, and 14 women with 20 benign lesions.

In vivo magnetic resonance imaging of the estrogen receptor in an orthotopic model of human breast cancer.

Histologic overexpression of the estrogen receptor α (ER) is a well-established prognostic marker in breast cancer. Noninvasive imaging techniques that could detect ER overexpression would be useful in a variety of settings where patients' biopsies are problematic to obtain. This study focused on developing, by in vivo MRI, strategies to measure the level of ER expression in an orthotopic mouse model of human breast cancer.

Structure of estradiol metal chelate and estrogen receptor complex: the basis for designing a new class of selective estrogen receptor modulators.

Selective estrogen receptor modulators, such as 17β-estradiol derivatives bound to metal complexes, have been synthesized as targeted probes for the diagnosis and treatment of breast cancer. Here, we report the detailed 3D structure of estrogen receptor α ligand-binding domain (ERα-LBD) bound with a novel estradiol-derived metal complex, estradiol-pyridine tetra acetate europium(III), at 2.6 Å resolution.

Triple-negative breast cancer: present challenges and new perspectives.

Triple-negative breast cancers (TNBC), characterized by absence of estrogen receptor (ER), progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), are typically associated with poor prognosis, due to aggressive tumor phenotype(s), only partial response to chemotherapy and present lack of clinically established targeted therapies. Advances in the design of individualized strategies for treatment of TNBC patients require further elucidation, by combined 'omics' approaches, of the molecular mechanisms underlying TNBC phenotypic heterogeneity, and the still poorly understood association of TNBC with BRCA1 mutations. An overview is here presented on TNBC profiling in terms of expression signatures, within the functional genomic breast tumor classification, and ongoing efforts toward identification of new therapy targets and bioimaging markers.

Principal component analysis of dynamic contrast enhanced MRI in human prostate cancer.

Objectives: To develop and evaluate a fast, objective and standardized method for image processing of dynamic contrast enhanced MRI of the prostate based on principal component analysis (PCA).

Materials And Methods: The study was approved by the institutional internal review board; signed informed consent was obtained. MRI of the prostate at 3 Tesla was performed in 21 patients with biopsy proven cancers before radical prostatectomy.

Principal component analysis of breast DCE-MRI adjusted with a model-based method.

Purpose: To investigate a fast, objective, and standardized method for analyzing breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) applying principal component analysis (PCA) adjusted with a model-based method.

Materials And Methods: 3D gradient-echo DCE breast images of 31 malignant and 38 benign lesions, recorded on a 1.5T scanner, were retrospectively analyzed by PCA and by the model-based three-timepoints (3TP) method.

Kinetics of hyperpolarized 13C1-pyruvate transport and metabolism in living human breast cancer cells.

Metabolic fluxes can serve as specific biomarkers for detecting malignant transformations, tumor progression, and response to microenvironmental changes and treatment procedures. We present noninvasive hyperpolarized (13)C NMR investigations on the metabolic flux of pyruvate to lactate, in a well-controlled injection/perfusion system using T47D human breast cancer cells. Initial rates of pyruvate-to-lactate conversion were obtained by fitting the hyperpolarized (13)C and ancillary (31)P NMR data to a model, yielding both kinetic parameters and mechanistic insight into this conversion.

Magnetization transfer magic-angle-spinning z-spectroscopy of excised tissues.

NMR experiments devised to aid in analyses of tissues include magnetization transfer (MT), which can highlight the signals of biological macromolecules through cross-relaxation and/or chemical exchange processes with the bulk (1)H water resonance, and high-resolution magic-angle-spinning (HRMAS) methods, akin to those used in solid-state NMR to introduce additional spectral resolution via the averaging of spin anisotropies. This paper explores the result of combining these methodologies, and reports on MT "z-spectroscopy" between water and cell components in excised tissues under a variety of HRMAS conditions. Main features arising from the resulting (1)H "MTMAS" experiments include strong spinning sideband manifolds centered at the liquid water shift, high-resolution isotropic features coinciding with aliphatic and amide proton resonances, and a second sideband manifold arising as spinning speeds are increased.

Estrogen regulation of vascular endothelial growth factor in breast cancer in vitro and in vivo: the role of estrogen receptor alpha and c-Myc.

The role of c-Myc in estrogen regulation of vascular endothelial growth factor (VEGF) and of the vasculature function has been investigated in breast cancer cells and tumors. The studies were performed on MCF7 wild-type cells and MCF7-35im clone, stably transfected with an inducible c-Myc gene. In vitro and ex vivo methods for investigating molecular events were integrated with in vivo magnetic resonance imaging of the vascular function.

Non-invasive imaging of barriers to drug delivery in tumors.

Solid tumors often develop high interstitial fluid pressure (IFP) as a result of increased water leakage and impaired lymphatic drainage, as well as changes in the extracellular matrix composition and elasticity. This high fluid pressure forms a barrier to drug delivery and hence, resistance to therapy. We have developed techniques based on contrast enhanced magnetic resonance imaging for mapping in tumors the vascular and transport parameters determining the delivery efficiency of blood borne substances.

Model-based and model-free parametric analysis of breast dynamic-contrast-enhanced MRI.

A wide range of dynamic-contrast-enhanced (DCE) sequences and protocols, image processing methods, and interpretation criteria have been developed and evaluated over the last 20 years. In particular, attempts have been made to better understand the origin of the contrast observed in breast lesions using physiological models that take into account the vascular and tissue-specific features that influence tracer perfusion. In addition, model-free algorithms to decompose enhancement patterns in order to segment and classify different breast tissue types have been developed.