Assessment of regional sacral bone quality: A step towards patient-specific fracture fixation.

Characterizing changes in sacral bone density could help us to inform instrumentation choices for procedures involving the sacrum. The aim of this study is to provide detailed maps of changes in sacral bone density across a series of patients using opportunistic quantitative computed tomography (QCT). We hypothesized that there would be significant differences in local cortical and trabecular bone density associated with age and sex. Fifty-four three-dimensional sacral models were segmented from routine clinical computed tomography scans, and detailed bone density estimates were derived for each bone using a calibrated opportunistic QCT approach. The effects of age and sex on cortical and trabecular bone density were determined across the sample. Overall cortical bone loss averaged 2.1 and 0.9 mg/cc per year, and trabecular bone loss was 1.6 and 0.7 mg/cc for female and males, respectively. Several regions had loss rates several times greater. Areas that were significantly affected by age included the vertebral bodies, bilateral ala, apex, and areas adjacent to both the anterior and posterior sacral foramina. Areas that were significantly affected by sex were the anterior sacral promontory, aspects of the ala. Bone density distribution across the sacrum changes nonuniformly due to factors including sex and age. Despite these overall trends, there remains significant variability between individuals. Clinical significance: This study provides detailed bone density information for both cortical and trabecular bone that could assist orthopaedic surgeons in planning surgical approaches to sacral fracture fixation.

Quantification and visualization of anterior pelvis bone density to optimize screw fixation: A novel technique.

Plate fixation of anterior pelvic ring fractures is often a vital component when surgically treating unstable pelvis fractures. Certain plate and screw configurations can have premature implant loosening, potentially in part due to insufficient pullout strength in lower density bone. This study sought to define densities about the anterior pelvic ring using a novel computer-based technique. Thirty-three patients who received a computed tomography (CT) of the abdomen/pelvis for reasons other than pelvis fracture in a 1-month time period were included. Three statistically distinct density regions of the anterior pelvis were identified based on the three-dimensional (3D) density map. The densest regions included both the anterior and posterior aspects of the superior pubic ramus, along with the region of bone along the inferior cotyloid fossa. The intermediate density region included the caudal and medial pubic body. The least dense region included the anterior aspect of the inferior pubic ramus (IPR), the posterior pubic body, and the posterior/inferior IPR. This study presents specific quantification of anterior pelvis bone density based on a novel technique using opportunistic CT scans. Clinical Significance: Anterior surgical fixation of unstable pelvic ring injuries may benefit from targeting areas of higher density as described in this novel technique.

Next-Generation Cancer Magnetic Resonance Imaging With Tumor-Targeted Alkylphosphocholine Metal Analogs.

OBJECTIVES: In an effort to exploit the elevated need for phospholipids displayed by cancer cells relative to normal cells, we have developed tumor-targeted alkylphosphocholines (APCs) as broad-spectrum cancer imaging and therapy agents. Radioactive APC analogs have exhibited selective uptake and prolonged tumor retention in over 50 cancer types in preclinical models, as well as over 15 cancer types in over a dozen clinical trials. To push the structural limits of this platform, we recently added a chelating moiety capable of binding gadolinium and many other metals for cancer-targeted magnetic resonance imaging (MRI), positron emission tomography imaging, and targeted radionuclide therapy. The aim of this work was to synthesize, characterize, and validate the tumor selectivity of a new broad-spectrum, tumor-targeted, macrocyclic MRI chelate, Gd-NM600, in xenograft and orthotopic tumor models. A secondary aim was to identify and track the in vivo chemical speciation and spatial localization of this new chelate Gd-NM600 in order to assess its Gd deposition properties. MATERIALS AND METHODS: T1 relaxivities of Gd-NM600 were characterized in water and plasma at 1.5 T and 3.0 T. Tumor uptake and subcellular localization studies were performed using transmission electron microscopy. We imaged 8 different preclinical models of human cancer over time and compared the T1-weighted imaging results to that of a commercial macrocyclic Gd chelate, Gd-DOTA. Finally, matrix-assisted laser desorption and ionization-mass spectrometry imaging was used to characterize and map the tissue distribution of the chemical species of Gd-NM600. RESULTS: Gd-NM600 exhibits high T1 relaxivity (approximately 16.4 s-1/mM at 1.5 T), excellent tumor uptake (3.95 %ID/g at 48 hours), prolonged tumor retention (7 days), and MRI conspicuity. Moreover, minimal tumor uptake saturability of Gd-NM600 was observed. Broad-spectrum tumor-specific uptake was demonstrated in 8 different human cancer models. Cancer cell uptake of Gd-NM600 via endosomal internalization and processing was revealed with transmission electron microscopy. Importantly, tissue mass spectrometry imaging successfully interrogated the spatial localization and chemical speciation of Gd compounds and also identified breakdown products of Gd species. CONCLUSIONS: We have introduced a new macrocyclic cancer-targeted Gd chelate that achieves broad-spectrum tumor uptake and prolonged retention. Furthermore, we have demonstrated in vivo stability of Gd-NM600 by ultrahigh resolution MS tissue imaging. A tumor-targeted contrast agent coupled with the enhanced imaging resolution of MRI relative to positron emission tomography may transform oncologic imaging.

Sources of error in bone mineral density estimates from quantitative CT.

Bone mineral density (BMD) estimates from quantitative computed tomography (QCT) have proven useful for opportunistic screening of osteoporosis, treatment monitoring, and bone strength measurement. These estimates are subject to bias and variance from a variety of sources related to the imaging equipment, methods applied in the estimation procedure, and the patients themselves. In this article, we review the literature to describe the sources and sizes of error in spine and hip BMD estimates from single-energy QCT that can result from factors related to the scanner, imaging techniques, imaging subject, calibration phantom, and calibration approach. We also describe the baseline variance that can be expected based on repeatability and reproducibility studies. Though reproducible BMD estimates may be achievable with QCT, a thorough understanding of the potential sources of error and their size relative to the diagnostic task is essential to their appropriate and meaningful interpretation.

Changes in scapular bone density vary by region and are associated with age and sex.

BACKGROUND: Decreases in bone density of the scapula due to age and disease can make orthopedic procedures such as arthroplasty and fracture fixation challenging. There is limited information in the literature regarding the effect of age and sex on the patterns of these density changes across the bone. Characterizing these changes could assist the surgeon in planning optimal instrumentation placement. METHODS: Ninety-seven 3-dimensional models of the scapula were segmented from routine clinical computed tomography scans, and an opportunistic quantitative computed tomography approach was used to obtain detailed calibrated bone density measurements for each bone model. The effects of age and sex on cortical and trabecular bone density were assessed for the entire scapula. Specific regions (eg, scapular spine) where these factors had a significant effect were identified. Three-dimensional models were generated to allow clear visualization of the changes in density patterns. RESULTS: Cortical bone loss averaged 1.0 mg/cm3 and 0.3 mg/cm3 per year for female and male subjects, respectively, and trabecular bone loss averaged 1.6 mg/cm3 and 1.2 mg/cm3, respectively. However, several regions had loss rates several times greater. Areas that were significantly affected by age included the acromion, scapular spine, base of the coracoid, inferior glenoid neck, and glenoid vault. Areas that were significantly affected by sex were the scapular spine and body. CONCLUSIONS: These findings provide evidence that the bone density distribution across the scapula changes non-uniformly because of factors including sex and age. Despite overall trends of bone loss, there remains significant variability between individuals, and subject-specific tools for planning surgical procedures in which scapular fixation is required may be beneficial.

The effect of age and sex on pelvic bone density measured opportunistically in clinical CT scans.

Unstable pelvic ring fractures are severe and complex injuries, and surgical fixation is challenging and can be complicated by early failure due in part to difficulties with securely fixing screws in low-density bone. There is limited information in the literature about how the density distribution across the pelvic bones changes with age and sex. In this study, we used 60 sets of calibrated bone density measurements obtained opportunistically from clinical computed tomography scans of the pelvis. Three-dimensional models of the innominate bone were produced and the effects of age and sex on cortical bone density modeled. Overall trends and regions where these factors had a significant effect were identified, and the results visualized. Across the entire innominate bone, the mean loss of density was found to be 1.6 mg/cc per year, with several specific areas (pubic body, iliac fossa, posterior ilium, and anterior inferior iliac spine for example) showing significant rates of loss up to three times greater than the rest of the bone. Areas significantly affected by sex included the posterior pubic root, anterior aspect of the pubic body, and iliac crest. Despite overall trends of attenuation, there remains significant variability between individuals. This supports the need to further explore subject-specific planning tools for pelvic fracture repair. Statement of clinical significance: Bone density changes across the innominate bone due to age and sex tend to vary between individuals, although consistent effects were seen at specific regions. This information may help in surgical planning of unstable fracture repairs.

Applying Artificial Intelligence to Mitigate Effects of Patient Motion or Other Complicating Factors on Image Quality.

Artificial intelligence, particularly deep learning, offers several possibilities to improve the quality or speed of image acquisition in magnetic resonance imaging (MRI). In this article, we briefly review basic machine learning concepts and discuss commonly used neural network architectures for image-to-image translation. Recent examples in the literature describing application of machine learning techniques to clinical MR image acquisition or postprocessing are discussed. Machine learning can contribute to better image quality by improving spatial resolution, reducing image noise, and removing undesired motion or other artifacts. As patients occasionally are unable to tolerate lengthy acquisition times or gadolinium agents, machine learning can potentially assist MRI workflow and patient comfort by facilitating faster acquisitions or reducing exogenous contrast dosage. Although artificial intelligence approaches often have limitations, such as problems with generalizability or explainability, there is potential for these techniques to improve diagnostic utility, throughput, and patient experience in clinical MRI practice.

Practical Considerations for Radiologists in Implementing a Patient-friendly MRI Experience.

For many patients, numerous unpleasant features of the magnetic resonance imaging (MRI) experience such as scan duration, auditory noise, spatial confinement, and motion restrictions can lead to premature termination or low diagnostic quality of imaging studies. This article discusses practical, patient-oriented considerations that are helpful for radiologists contemplating ways to improve the MRI experience for patients. Patient friendly scanner properties are discussed, with an emphasis on literature findings of effectiveness in mitigating patient claustrophobia, other anxiety, or motion and on reducing scan incompletion rates or need for sedation. As shorter scanning protocols designed to answer specific diagnostic questions may be more practical and tolerable to the patient than a full-length standard-of-care examination, a few select protocol adjustments potentially useful for specific clinical settings are discussed. In addition, adjunctive devices such as audiovisual or other sensory aides that can be useful distractive approaches to reduce patient discomfort are considered. These modifications to the MRI scanning process not only allow for a more pleasant experience for patients, but they may also increase patient compliance and decrease patient movement to allow more efficient acquisition of diagnostic-quality images.

Making Magnets More Attractive: Physics and Engineering Contributions to Patient Comfort in MRI.

Patient comfort is an important factor of a successful magnetic resonance (MR) examination, and improvements in the patient's MR scanning experience can contribute to improved image quality, diagnostic accuracy, and efficiency in the radiology department, and therefore reduced cost. Magnet designs that are more open and accessible, reduced auditory noise of MR examinations, light and flexible radiofrequency (RF) coils, and faster motion-insensitive imaging techniques can all significantly improve the patient experience in MR imaging. In this work, we review the design, development, and implementation of these physics and engineering approaches to improve patient comfort.

A General Framework for Monitoring Image Acquisition Workflow in the Radiology Environment: Timeliness for Acute Stroke CT Imaging.

Many facets of an image acquisition workflow leave a digital footprint, making workflow analysis amenable to an informatics-based solution. This paper describes a detailed framework for analyzing workflow and uses acute stroke response timeliness in CT as a practical demonstration. We review methods for accessing the digital footprints resulting from common technologist/device interactions. This overview lays a foundation for obtaining data for workflow analysis. We demonstrate the method by analyzing CT imaging efficiency in the setting of acute stroke. We successfully used digital footprints of CT technologists to analyze their workflow. We presented an overview of other digital footprints including but not limited to contrast administration, patient positioning, billing, reformat creation, and scheduling. A framework for analyzing image acquisition workflow was presented. This framework is transferable to any modality, as the key steps of image acquisition, image reconstruction, image post processing, and image transfer to PACS are common to any imaging modality in diagnostic radiology.

Intrathecal antibody distribution in the rat brain: surface diffusion, perivascular transport and osmotic enhancement of delivery.

KEY POINTS: It is unclear precisely how macromolecules (e.g. endogenous proteins and exogenous immunotherapeutics) access brain tissue from the cerebrospinal fluid (CSF). We show that transport at the brain-CSF interface involves a balance between Fickian diffusion in the extracellular spaces at the brain surface and convective transport in perivascular spaces of cerebral blood vessels. Intrathecally-infused antibodies exhibited size-dependent access to the perivascular spaces and tunica media basement membranes of leptomeningeal arteries. Perivascular access and distribution of full-length IgG could be enhanced by intrathecal co-infusion of hyperosmolar mannitol. Pores or stomata present on CSF-facing leptomeningeal cells ensheathing blood vessels in the subarachnoid space may provide unique entry sites into the perivascular spaces from the CSF. These results illuminate new mechanisms likely to govern antibody trafficking at the brain-CSF interface with relevance for immune surveillance in the healthy brain and insights into the distribution of therapeutic antibodies. ABSTRACT: The precise mechanisms governing the central distribution of macromolecules from the cerebrospinal fluid (CSF) to the brain and spinal cord remain poorly understood, despite their importance for physiological processes such as antibody trafficking for central immune surveillance, as well as several ongoing intrathecal clinical trials. In the present study, we clarify how IgG and smaller single-domain antibodies (sdAb) distribute throughout the whole brain in a size-dependent manner after intrathecal infusion in rats using ex vivo fluorescence and in vivo three-dimensional magnetic resonance imaging. Antibody distribution was characterized by diffusion at the brain surface and widespread distribution to deep brain regions along the perivascular spaces of all vessel types, with sdAb accessing a four- to seven-fold greater brain area than IgG. Perivascular transport involved blood vessels of all caliber and putative smooth muscle and astroglial basement membrane compartments. Perivascular access to smooth muscle basement membrane compartments also exhibited size-dependence. Electron microscopy was used to show stomata on leptomeningeal coverings of blood vessels in the subarachnoid space as potential access points allowing substances in the CSF to enter the perivascular space. Osmolyte co-infusion significantly enhanced perivascular access of the larger antibody from the CSF, with intrathecal 0.75 m mannitol increasing the number of perivascular profiles per slice area accessed by IgG by ∼50%. The results of the present study reveal potential distribution mechanisms for endogenous IgG, which is one of the most abundant proteins in the CSF, as well as provide new insights with respect to understanding and improving the drug delivery of macromolecules to the central nervous system via the intrathecal route.

Uptake and retention of manganese contrast agents for PET and MRI in the rodent brain.

Manganese-enhanced magnetic resonance imaging (MRI) is an established neuroimaging method for signal enhancement, tract tracing, and functional studies in rodents. Along with the increasing availability of combined positron emission tomography (PET) and MRI scanners, the recent development of the positron-emitting isotope 52 Mn has prompted interest in the use of Mn2+ as a dual-modality contrast agent. In this work, we characterized and compared the uptake of systemically delivered Mn2+ and radioactive 52 Mn2+ in the rat brain for MRI and PET, respectively. Additionally, we examined the biodistribution of two formulations of 52 Mn2+ in the rat. In MRI, maximum uptake was observed one day following delivery of the highest MnCl2 dose tested (60 mg/kg), with some brain regions showing delayed maximum enhancement 2-4 days following delivery. In PET, we observed low brain uptake after systemic delivery, with a maximum of approximately 0.2% ID/g. We also studied the effect of final formulation vehicle (saline compared with MnCl2 ) on 52 Mn2+ organ biodistribution and brain uptake. We observed that the addition of bulk Mn2+ carrier to 52 Mn2+ in solution resulted in significantly reduced 52 Mn2+ uptake in the majority of organs, including the brain. These results lay the groundwork for further development of 52 Mn PET or dual Mn-enhanced PET-MR neuroimaging in rodents, and indicate several interesting potential applications of 52 Mn PET in other organs and systems. Copyright © 2016 John Wiley & Sons, Ltd.