PET/MRI and Bioluminescent Imaging Identify Hypoxia as a Cause of Programmed Cell Death Ligand 1 Image Heterogeneity.

Purpose To examine the association between hypoxia and programmed cell death ligand 1 (PD-L1) expression using bioluminescence imaging (BLI) and PET/MRI in a syngeneic mouse model of triple-negative breast cancer (TNBC). Materials and Methods PET/MRI and optical imaging were used to determine the role of hypoxia in altering PD-L1 expression using a syngeneic TNBC model engineered to express luciferase under hypoxia. Results Imaging showed a close spatial association between areas of hypoxia and increased PD-L1 expression in the syngeneic murine (4T1) tumor model.

Multi-Site Concordance of Diffusion-Weighted Imaging Quantification for Assessing Prostate Cancer Aggressiveness.

Background: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease.

Purpose: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms.

Study Type: Prospective.

The Ponticulus Ethmoidalis: A Newly Appreciated Anatomic Landmark in Endoscopic Sinus Surgery.

Introduction: Ethmoid sinus anatomy is so variable it has been referred to as a "labyrinth." Accordingly, this provides a challenge for surgeons performing ethmoidectomy. Identifying consistent anatomic features or landmarks within the ethmoid sinus can aid surgeons performing sinus surgery.

Neural-network classification of cardiac disease from P cardiovascular magnetic resonance spectroscopy measures of creatine kinase energy metabolism.

Background: The heart's energy demand per gram of tissue is the body's highest and creatine kinase (CK) metabolism, its primary energy reserve, is compromised in common heart diseases. Here, neural-network analysis is used to test whether noninvasive phosphorus (P) cardiovascular magnetic resonance spectroscopy (CMRS) measurements of cardiac adenosine triphosphate (ATP) energy, phosphocreatine (PCr), the first-order CK reaction rate k, and the rate of ATP synthesis through CK (CK flux), can predict specific human heart disease and clinical severity.

Methods: The data comprised the extant 178 complete sets of PCr and ATP concentrations, k, and CK flux data from human CMRS studies performed on clinical 1.

Republished: Real-time MRI guidance for intra-arterial drug delivery in a patient with a brain tumor: technical note.

Patients suffering from malignant brain tumors are burdened with a grim prognosis. The blood brain barrier is considered a primary obstacle in therapeutic drug delivery to the brain. Intra-arterial (IA) delivery of therapeutic agents following osmotic BBB opening has been attempted for years, but high variability has limited its widespread implementation.

Noninvasive Monitoring of Allogeneic Stem Cell Delivery with Dual-Modality Imaging-Visible Microcapsules in a Rabbit Model of Peripheral Arterial Disease.

Stem cell therapies, although promising for treating peripheral arterial disease (PAD), often suffer from low engraftment rates and the inability to confirm the delivery success and track cell distribution and engraftment. Stem cell microencapsulation combined with imaging contrast agents may provide a means to simultaneously enhance cell survival and enable cell tracking with noninvasive imaging. Here, we have evaluated a novel MRI- and X-ray-visible microcapsule formulation for allogeneic mesenchymal stem cell (MSC) delivery and tracking in a large animal model.

Multi-level otsu method to define metabolic tumor volume in positron emission tomography.

This study was to validate reliability and clinical utility of a PET tumor segmentation method using multi-level Otsu (MO-PET) in standard National Electrical Manufacturers Association (NEMA) image quality (IQ) phantom and patients with osteosarcoma. The NEMA IQ phantom was prepared with a lesion-to-background ratio (LBR) of either 8:1, 4:1, or 1.5:1.

Real-time MRI guidance for intra-arterial drug delivery in a patient with a brain tumor: technical note.

Patients with malignant brain tumors have a poor prognosis. The blood-brain barrier (BBB) is considered a primary obstacle in therapeutic drug delivery to the brain. Intra-arterial (IA) delivery of therapeutic agents following osmotic BBB opening has been attempted for years, but high variability has limited its widespread implementation.

Novel Observations of Female Genital Anatomy in Classic Bladder Exstrophy Using 3-Dimensional Magnetic Resonance Imaging Reconstruction.

Purpose: Understanding the distinct female anatomy in classic bladder exstrophy is crucial for optimal reconstructive and functional outcomes. We present novel quantitative anatomical data in females with classic bladder exstrophy before primary closure.

Materials And Methods: 3-Dimensional reconstruction was performed in patients undergoing pelvic magnetic resonance imaging, and pelvic anatomy was characterized, including measurements of the vagina, cervix and erectile bodies.

Current Methods to Define Metabolic Tumor Volume in Positron Emission Tomography: Which One is Better?

Numerous methods to segment tumors using F-fluorodeoxyglucose positron emission tomography (FDG PET) have been introduced. Metabolic tumor volume (MTV) refers to the metabolically active volume of the tumor segmented using FDG PET, and has been shown to be useful in predicting patient outcome and in assessing treatment response. Also, tumor segmentation using FDG PET has useful applications in radiotherapy treatment planning.

Toward uniform implementation of parametric map Digital Imaging and Communication in Medicine standard in multisite quantitative diffusion imaging studies.

This paper reports on results of a multisite collaborative project launched by the MRI subgroup of Quantitative Imaging Network to assess current capability and provide future guidelines for generating a standard parametric diffusion map Digital Imaging and Communication in Medicine (DICOM) in clinical trials that utilize quantitative diffusion-weighted imaging (DWI). Participating sites used a multivendor DWI DICOM dataset of a single phantom to generate parametric maps (PMs) of the apparent diffusion coefficient (ADC) based on two models. The results were evaluated for numerical consistency among models and true phantom ADC values, as well as for consistency of metadata with attributes required by the DICOM standards.

Multisite concordance of apparent diffusion coefficient measurements across the NCI Quantitative Imaging Network.

Diffusion weighted MRI has become ubiquitous in many areas of medicine, including cancer diagnosis and treatment response monitoring. Reproducibility of diffusion metrics is essential for their acceptance as quantitative biomarkers in these areas. We examined the variability in the apparent diffusion coefficient (ADC) obtained from both postprocessing software implementations utilized by the NCI Quantitative Imaging Network and online scan time-generated ADC maps.

Comparison of novel multi-level Otsu (MO-PET) and conventional PET segmentation methods for measuring FDG metabolic tumor volume in patients with soft tissue sarcoma.

Background: We have previously developed a novel and highly consistent PET segmentation algorithm using a multi-level Otsu method (MO-PET). The aim of this study was to evaluate the reliability of MO-PET compared to conventional PET segmentation methods for measuring F-FDG (FDG) PET metabolic tumor volume (MTV) in patients with soft tissue sarcoma (STS). Clinical and imaging data were obtained from the Cancer Imaging Archive.

Breast cancer cell cyclooxygenase-2 expression alters extracellular matrix structure and function and numbers of cancer associated fibroblasts.

Cyclooxygenase-2 (COX-2) is a critically important mediator of inflammation that significantly influences tumor angiogenesis, invasion, and metastasis. We investigated the role of COX-2 expressed by triple negative breast cancer cells in altering the structure and function of the extracellular matrix (ECM). COX-2 downregulation effects on ECM structure and function were investigated using magnetic resonance imaging (MRI) and second harmonic generation (SHG) microscopy of tumors derived from triple negative MDA-MB-231 breast cancer cells, and a derived clone stably expressing a short hairpin (shRNA) molecule downregulating COX-2.

Structure and Function of a Prostate Cancer Dissemination-Permissive Extracellular Matrix.

The poor prognosis of metastatic prostate cancer continues to present a major challenge in prostate cancer treatment. The tumor extracellular matrix (ECM) plays an important role in facilitating metastasis. Here, we investigated the structure and function of an ECM that facilitates prostate cancer metastasis by comparing orthotopic tumors that frequently metastasize to poorly metastatic subcutaneous tumors.

Collagen fibers mediate MRI-detected water diffusion and anisotropy in breast cancers.

Collagen 1 (Col1) fibers play an important role in tumor interstitial macromolecular transport and cancer cell dissemination. Our goal was to understand the influence of Col1 fibers on water diffusion, and to examine the potential of using noninvasive diffusion tensor imaging (DTI) to indirectly detect Col1 fibers in breast lesions. We previously observed, in human MDA-MB-231 breast cancer xenografts engineered to fluoresce under hypoxia, relatively low amounts of Col1 fibers in fluorescent hypoxic regions.

Choline kinase-α protein and phosphatidylcholine but not phosphocholine are required for breast cancer cell survival.

High levels of total choline and phosphocholine (PC) are consistently observed in aggressive cancers. Choline kinase (Chk) catalyzes choline phosphorylation to produce PC in phosphatidylcholine (PtdCho) biosynthesis. PtdCho is the most abundant phospholipid in eukaryotic cell membranes and plays a dual role as the structural component of membranes and as a substrate to produce lipid second messengers such as phosphatidic acid and diacylglycerol.

Fused X-ray and MR imaging guidance of intrapericardial delivery of microencapsulated human mesenchymal stem cells in immunocompetent swine.

Purpose: To assess intrapericardial delivery of microencapsulated, xenogeneic human mesenchymal stem cells (hMSCs) by using x-ray fused with magnetic resonance (MR) imaging (x-ray/MR imaging) guidance as a potential treatment for ischemic cardiovascular disease in an immunocompetent swine model.

Materials And Methods: All animal experiments were approved by the institutional animal care and use committee. Stem cell microencapsulation was performed by using a modified alginate-poly-l-lysine-alginate encapsulation method to include 10% (wt/vol) barium sulfate to create barium-alginate microcapsules (BaCaps) that contained hMSCs.

Using C-arm x-ray imaging to guide local reporter probe delivery for tracking stem cell engraftment.

Poor cell survival and difficulties with visualization of cell delivery are major problems with current cell transplantation methods. To protect cells from early destruction, microencapsulation methods have been developed. The addition of a contrast agent to the microcapsule also could enable tracking by MR, ultrasound, and X-ray imaging.

Hypoxic tumor environments exhibit disrupted collagen I fibers and low macromolecular transport.

Hypoxic tumor microenvironments result in an aggressive phenotype and resistance to therapy that lead to tumor progression, recurrence, and metastasis. While poor vascularization and the resultant inadequate drug delivery are known to contribute to drug resistance, the effect of hypoxia on molecular transport through the interstitium, and the role of the extracellular matrix (ECM) in mediating this transport are unexplored. The dense mesh of fibers present in the ECM can especially influence the movement of macromolecules.

Collagen I fiber density increases in lymph node positive breast cancers: pilot study.

Collagen I (Col1) fibers are a major structural component in the extracellular matrix of human breast cancers. In a preliminary pilot study, we explored the link between Col1 fiber density in primary human breast cancers and the occurrence of lymph node metastasis. Col1 fibers were detected by second harmonic generation (SHG) microscopy in primary human breast cancers from patients presenting with lymph node metastasis (LN+) versus those without lymph node metastasis (LN-).

Hypoxia regulates CD44 and its variant isoforms through HIF-1α in triple negative breast cancer.

Background: The CD44 transmembrane glycoproteins play multifaceted roles in tumor progression and metastasis. CD44 expression has also been associated with stem-like breast cancer cells. Hypoxia commonly occurs in tumors and is a major cause of radiation and chemo-resistance.

Evaluation of pelvic floor muscular redistribution after primary closure of classic bladder exstrophy by 3-dimensional magnetic resonance imaging.

Purpose: We used 3-dimensional magnetic resonance imaging reconstruction to generate models of the pelvic floor musculature in classic bladder exstrophy, allowing for statistical analysis of changes seen in the anatomy after primary closure.

Materials And Methods: Patients with classic bladder exstrophy underwent pelvic magnetic resonance imaging before and after primary closure. Contours of the levator ani were mapped and measured in 3-dimensional space.