Contrast Agent Research Articles

Comparing DCE-MRI and DSA: Understanding the embolization of hypervascular spinal metastases.

This study aims to examine and compare the effectiveness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and Digital Subtraction Angiography (DSA) in evaluating hypervascular spinal metastases. A comprehensive literature review was conducted, utilizing top-tier databases such as PubMed, Scopus and Google Scholar, to compile an authoritative and up-to-date overview of the current advancements in the field. We synthesized key studies focusing on the advantages, limitations and efficacy of both imaging techniques. DCE-MRI provides a non-invasive method for evaluating tissue morphology, perfusion and vascularity, offering valuable information for cancer diagnosis and treatment monitoring. In contrast, DSA is an invasive procedure primarily used for embolization and diagnosing cerebrovascular events. Both modalities have distinct features regarding image acquisition, contrast agents, resolution and accessibility. DCE-MRI shows promise for cancer-related applications, offering advantages over conventional MRI by incorporating anatomical and hemodynamic parameters. While DSA remains important for cases requiring critical vascular information, further research is necessary to explore its potential therapeutic benefits in assessing vessel patency. Continued investigations are crucial to uncover additional insights and therapeutic applications for both DCE-MRI and DSA in medical imaging.

BIOM-23. DEUTERIUM METABOLIC IMAGING OF RESPONSE TO PRECISION THERAPY IN BRAF-V600E MUTANT GLIOMAS

Abstract Oncogenic BRAF-V600E mutations are frequently observed in low- and high-grade gliomas in adults and children. BRAF transduces signals from receptor tyrosine kinases to downstream effectors such as MEK1/2 and ERK, which regulate both metabolism and proliferation. The combination of the BRAF-V600E inhibitor dabrafenib and the MEK1/2 inhibitor trametinib (Dab/Tra) improves patient survival. However, there is considerable variation in the durability of response, underscoring the need for early biomarkers of treatment response. Magnetic resonance imaging (MRI), which is the gold standard for patient management, does not reliably assess response to therapy. Since the BRAF/MEK pathway regulates metabolism, the goal of this study was to determine whether Dab/Tra induces alterations in glucose metabolism that can be leveraged for non-invasive imaging. Using gene expression profiling, in vivo metabolomics, and stable isotope tracing, we show that Dab/Tra downregulates glucose metabolism to lactate in human and murine BRAF-V600E mutant models (AM38, 2341). In vivo infusion with [U-13C]-glucose in mice bearing intracranial AM38 tumors confirmed that Dab/Tra downregulates glucose metabolism to lactate in the tumor in vivo. Mechanistically, Dab/Tra destabilizes hypoxia inducible factor-1a and downregulates glycolytic genes, including SLC2A1, HK2, PFKFB3, and LDHA. Deuterium metabolic imaging (DMI) is a novel, clinical stage method of tracing glucose metabolism in vivo. Our studies show that lactate production from [6,6-2H]-glucose is reduced in AM38 and 2341 cells treated with Dab/Tra. Importantly, lactate production is reduced within 48 h of treatment with Dab/Tra in mice bearing intracranial AM38 tumors at the clinical magnetic field strength of 3T. Furthermore, this drop in 2H-lactate production is observed in the absence of MRI-detectable volumetric alterations and is predictive of extended survival. Collectively, our studies mechanistically link BRAF/MEK inhibition with downregulation of glycolysis and identify [6,6’-2H]-glucose as a novel contrast agent for imaging early response to therapy. Clinical translation of our studies will enable precision imaging of response to therapy for patients with BRAF-mutant gliomas.

NIMG-19. DEUTERIUM METABOLIC IMAGING INTERROGATES THE HISTONE H3K27M MUTATION AND PROVIDES AN EARLY READOUT OF RESPONSE TO THERAPY IN DIFFUSE MIDLINE GLIOMAS

Abstract Diffuse midline gliomas (DMGs) are lethal primary brain tumors in children that are driven by recurrent lysine 27 to methionine mutations in histone H3 (H3K27M). Radiation is standard of care and the imipridones ONC201 and ONC206 have emerged as promising therapies for DMG patients. Although magnetic resonance imaging (MRI) is the mainstay for patient management, it does not reliably assess response to therapy. Therefore, the goal of this study was to identify metabolic alterations induced by H3K27M that can be leveraged for non-invasive metabolic imaging of DMGs. Using patient-derived (BT245, SF8628, SF7761, SU-DIPG-6, DIPG7, SU-DIPG-13) and syngeneic (26-B7, 26-C2) models, we show that the H3K27M mutation upregulates glucose metabolism via glycolysis to lactate. Silencing the H3K27M mutation reduces glycolytic capacity and depletes lactate, an effect that is associated with downregulation of rate-limiting glycolytic enzymes and transporters (SLC2A1, HK2, PFKFB3, PGK1, SLC16A3). Deuterium metabolic imaging (DMI) is a novel, clinical stage method of tracing glucose metabolism in vivo. Our studies show that lactate production from [6,6-2H]-glucose is spatially localized to tumor vs. normal brain in mice bearing intracranial BT245, SF8628 or 26-B7 xenografts at clinical magnetic field strength (3T). Lactate production from [6,6’-2H]-glucose is reduced in patient-derived (BT245, SF8628, SF7761) or syngeneic (26-B7) cells treated with radiation, ONC201 or ONC206. Importantly, lactate production is reduced at an early timepoint (5 days) following treatment with ONC206, when changes cannot be detected by MRI, in mice bearing intracranial BT245 or SF8628 xenografts. Collectively, our studies link the H3K27M mutation with elevated glycolysis and identify [6,6’-2H]-glucose as a safe, orally administered contrast agent for visualizing the metabolically active lesion and for imaging early response to therapy in DMGs in vivo. Clinical translation of our studies will provide physicians with a much-needed tool to determine whether DMG patients are responding to standard and experimental therapies under development.

RADT-19. PILOT STUDY OF VELOCITY-SELECTIVE ARTERIAL SPIN LABEL MRI (VSASL-MRI) DERIVED RELATIVE CEREBRAL BLOOD FLOW TO DISTINGUISH IMAGING CHANGES AFTER RADIOSURGERY (SRS) FROM PROGRESSIVE BRAIN METASTASIS (BM)

Abstract Management of imaging progression on standard contrast enhanced MRI (cMRI) after SRS for brain metastasis is challenging as treatment effect/necrosis appears similar to progressive tumor. VSASL-MRI uses water labeled based on velocity, rather than spatial location, as an endogenous contrast agent and is therefore insensitive to transit delay impacting other ASL-MRI techniques. Other advantages include no IV contrast, limited susceptibility artifact, and absence of confounding leakage of gadolinium contrast into tissues. VSASL-MRI was performed (median 15 (4-123) months after SRS) to evaluate SRS treated solid tumor BM with clinician determined imaging progression on cMRI to evaluate the hypothesis that VSASL-MRI may distinguish biologic tumor (hyperperfused compared with normal brain) from treatment effect/necrosis (hypoperfused). 17 patients (19 progressing lesions) were enrolled. 13/19 index lesions had hypoperfusion. Of these, 3/13 had resection with no tumor present, 8/13 were conservatively managed and appeared to be treatment effect/necrosis as they stabilized or improved on follow-up cMRI without further BM directed intervention, and 2/13 had resection for further progression with active tumor present. For 6 index lesions that were hyperperfused: 3/6 had pathology were confirmed to be tumor, whereas the other 3/6 continued to progress (one got additional RT, two expired with progression). In addition, two pts had concurrent identification of new non-index previously untreated lesions on cMRI that were hyperperfused on VSASL-MRI and were treated. One of these patients had subsequent VSASL-MRI demonstrating post-SRS resolution of perfusion 2 months after treatment. This pilot data supports the hypothesis that VSASL-MRI may be useful in distinguishing tumor progression from radiation related imaging changes and/or be an early biomarker of radiosurgery response. We are initiating further study (1R01CA282928-01, PI; Qin) to refine the technique and prospectively assess the value of this approach in a larger number of patients.

NIMG-57. EMBEDDED GRAPH DERIVED FROM PSEUDO-RESTING-STATE FUNCTIONAL MRI CAN PREDICT COGNITIVE IMPAIRMENT IN GLIOMA

Abstract Resting-state brain network analyses are of great interest in studying the neurocognition and measuring the functional connectivity (FC) patterns of glioma patients. However, resting-state functional MRI (rs-fMRI) is not assessed in clinical routine due to the scan time and cost. The current study used pseudo-resting-state functional MRI (pseudo-rs-fMRI) derived from dynamic susceptibility contrast (DSC) perfusion MRI to predict cognitive impairment in glioma. 37 glioma patients were enrolled consecutively in the current study with DSC perfusion MRI acquired and neurocognition assessed, where 24 glioma patients also got rs-fMRI collected. The pseudo-rs-fMRI was created by voxel-wise subtracting the Gamma-variate modeled signal of contrast agent bolus from the original DSC perfusion signal. Following the pre-processing of pseudo-rs-fMRI and full rs-fMRI, the functional connectivity network (FCN) was established for each patient. Graph embedding was implemented to learn and extract features of each node in the binarized FCN, and the decision tree classification algorithm was applied to distinguish cognitive impairment. FCNs of 24 patients with DSC perfusion and rs-fMRI acquired were used to train the model, and FCNs of 13 patients with only DSC perfusion MRI acquired were used to test the model. The AUC (area under the receiver operating characteristic curve) was used to evaluate the model’s performance. The similarity and mean-square-difference between average FCNs extracted from rs-fMRI and pseudo-rs-fMRI were 0.6769 and 0.0263, respectively. Classifier trained using 24 FCNs of pseudo-rs-fMRI has an AUC of 0.750 in identifying cognitively impaired patients in the testing cohort. Combining FCNs of both rs-fMRI and pseudo-rs-fMRI to train the classifier resulted in a higher AUC of 0.833 in the testing cohort. To summary, DSC perfusion MRI-derived pseudo-rs-fMRI can be used to predict cognitive impairment in patients with gliomas. External validation would be required.

A collagenase-decorated Cu-based nanotheranostics: remodeling extracellular matrix for optimizing cuproptosis and MRI in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC), characterized by a dense extracellular matrix (ECM), presents significant therapeutic challenges due to its poor prognosis and high resistance to chemotherapy. Current chemodrugs and diagnostic agents largely fail to cross the barrier posed by the ECM, which severely limits the PDAC theranostics. This study introduces a novel theranostic strategy using thioether-hybridized hollow mesoporous organosilica nanoparticles (dsMNs) for the co-delivery of copper (Cu) and disulfiram (DSF), aiming to induce cuproptosis in PDAC cells. Our approach leverages the ECM-degrading enzyme collagenase, integrated with dsMNs, to enhance drug penetration by reducing matrix stiffness. Furthermore, the innovative use of a pancreatic cancer cell membrane coating on the nanoparticles enhances tumor targeting and stability (dsMCu-D@M-Co). The multifunctional platform not only facilitates deep drug penetration and triggers cuproptosis effectively but also utilizes the inherent properties of Cu to serve as a T1-weighted magnetic resonance imaging (MRI) contrast agent. In vitro and in vivo assessments demonstrate significant tumor size reduction in PDAC-bearing mice, highlighting the dual functionality of our platform in improving therapeutic efficacy and diagnostic precision. This integrated strategy represents a significant advancement in the management of PDAC, offering a promising new direction for overcoming one of the most lethal cancers.Graphical

Quantifying Lower Extremity Blood Flow using Low-Dose CT Perfusion: Validation in a swine model

Abstract Background Quantitative assessment of blood flow in peripheral extremities in conjunction with simultaneous CT angiography measurements can improve risk assessment and provide a critical decision-making tool for patients across a wide spectrum of vascular disease severity. Purpose This study assessed the reproducibility and accuracy of lower extremity blood flow measurements with a low-dose first-pass analysis CT perfusion technique. Materials and Methods This prospective study utilized 16 Yorkshire Swine to obtain lower extremity blood flow CT measurements at baseline and under induced femoral stenosis using a vascular occluder. Thirty-three pairs of CT measurements evaluated reproducibility, and 43 CT measurements assessed accuracy against ultrasound flow probe references. Contrast agent and saline chaser were both injected peripherally at a rate of 5 mL/s. Bolus tracking was used, and a pre-contrast and post-contrast helical scan were acquired at the base and approximately the peak of the femoral enhancement (CT angiogram), respectively. The acquired data were then used as analytical inputs into a first-pass analysis model to derive perfusion in mL/min/g. The reproducibility and accuracy of lower extremity perfusion measurements were assessed via Mixed model regression and Bland-Altman analysis. Results Calculated CT perfusion measurements derived from first-pass analysis technique (PCT), and the reference standard ultrasound perfusion measurements (Pref) were related by PCT = 1.06 Pref + 0.00 (r2= 0.90, Root-Mean-Square Error = 0.01 mL/min/g). The first (P1) and second (P2) CT perfusion measurements were related by P2 = 0.98 P1 + 0.02 (r = 0.97, Root-Mean-Square Error = 0.11 mL/min/g). The average effective dose of perfusion measurement using first-pass analysis technique was calculated to be only 2.13 mSv. Conclusion : The low-dose quantitative CT perfusion technique can accurately measure lower extremity perfusion (mL/min/g) using only two helical scans. The CT angiogram and perfusion measurements can be used as a comprehensive technique for morphological and physiological assessment of limb ischemia.

Safety of the contrast enhancement agent sulfur hexafluoride in ultrasound: Analysis of the Federal Drug Administration Adverse Event Reporting System database

ABSTRACT Background and Objectives Sulfur hexafluoride is an inert gas that creates microbubbles to enhance diagnostic accuracy in a variety of ultrasound (US) studies and is widely used in EUS. We analyzed the reported adverse events (AEs) of the US contrast agent, sulfur hexafluoride, extensively used during EUS procedures using a US national database. Methods From December 2008 to January 2024, AEs reported in the Federal Drug Administration Adverse Event Reporting System database for sulfur hexafluoride were examined. Results There were 1069 individual reports analyzed. Reports were excluded if they contained drugs other than sulfur hexafluoride. Echocardiogram (70.9%) was the common diagnostic study in which sulfur hexafluoride was administered. The most common AE reported was anaphylactic reaction (n = 179, 16.7%), followed by hypotension (n = 162, 15.2%), cardiac arrest (n = 161, 15.1%), and dyspnea (n = 159, 14.9%). The most common gastrointestinal AE was nausea (n = 135, 12.6%). Severity of AEs ranged from nonserious to death. Death associated with sulfur hexafluoride use was reported in 58 patients (5.4% of AE reports). Conclusions Anaphylactic reaction was the most common AE reported with sulfur hexafluoride use, and severe AEs including death may be more common than prior large, retrospective, observational studies to date have suggested.

Intestinal malrotation in newborns and infants: comparative possibilities of ultrasound and radiologic methods of investigation

BACKGROUND: Intestinal malrotation is a congenital pathology that results from abnormal fixation and rotation of the midgut during fetal development. This pathological condition is most often diagnosed during the first month of life and is often manifested by the presence of regurgitation, restlessness, vomiting with an admixture of bile, low weight gain. The narrow root of the mesentery facilitates the formation of midgut ingestion, which can lead to ischemia and necrosis and requires urgent surgical intervention. Ultrasound and radiologic examination with contrast are currently used to diagnose malrotation. AIM: To improve the diagnosis of intestinal malrotation in newborns and infants by carrying out a comparative analysis of the capabilities of radiologic and ultrasound methods of investigation when they are used in combination. MATERIALS AND METHODS: Data from 112 patients aged from 1 day from birth to 3 months 26 days between 2016 and 2024 with ultrasound signs of malrotation detected by microconvex and linear transducers were analyzed. 50 children were further followed up with this provisional or final diagnosis. Contrast agent passages and irrigographs were performed on an AXIOM Luminos DRF (Siemens), with 1 to 15 radiographs and up to 8 X-ray examination series obtained. RESULTS: The most common ultrasound sign of malrotation was atypical location of mesenteric vessels, and the most common radiologic sign was left-sided location of the colon and high standing of the cecum. Assessment of the location of the duodenojejunal junction was complicated in most cases. Surgery was performed in 17 children, one of them for suspected intestinal obstruction, and a ring-shaped pancreas was found in 4 patients. The diagnosis of malrotation was made in 40 children out of 50, in 4 cases this was discordant with the radiologic findings. Concomitant abnormal location of internal organs was detected in 12 patients. CONCLUSION: Screening ultrasound examination of all newborns should be considered as the pathology may be asymptomatic. It is important to include suspicion of malrotation in the diagnosis because of the possible manifestation of the pathology at a later age. It is currently not possible to completely abandon radiologic examination with contrast in the diagnosis of malrotation.

High‐resolution perfusion imaging in rodents using pCASL at 9.4 T

AbstractAdequate perfusion is critical for maintaining normal brain function and aberrations thereof are hallmarks of many diseases. Pseudo‐Continuous Arterial Spin Labeling (pCASL) MRI enables noninvasive quantitative perfusion mapping without contrast agent injection and with a higher signal‐to‐noise ratio (SNR) than alternative methods. Despite its great potential, pCASL remains challenging, unstable, and relatively low‐resolution in rodents – especially in mice – thereby limiting the investigation of perfusion properties in many transgenic or other relevant rodent models of disease. Here, we address this gap by developing a novel experimental setup for high‐resolution pCASL imaging in mice and combining it with the enhanced SNR of cryogenic probes. We show that our new experimental setup allows for optimal positioning of the carotids within the cryogenic coil, rendering labeling reproducible. With the proposed methodology, we managed to increase the spatial resolution of pCASL perfusion images by a factor of 15 in mice; a factor of 6 in rats is gained compared to the state of the art just by virtue of the cryogenic coil. We also show that the improved pCASL perfusion imaging allows much better delineation of specific brain areas, both in healthy animals as well as in rat and mouse models of stroke. Our results bode well for future high‐definition pCASL perfusion imaging in rodents.

Advancements in Tumor Diagnostics through Carbon Dot‐Assisted Photoacoustic Imaging

AbstractSerendipitously discovered, carbon dots (CDs) have attracted significant attention as a potential contrast agent for photoacoustic imaging (PAI) in the biomedical sector. CDs play an essential role in PAI, contributing significantly to the early detection of diseases and monitoring treatment progress, particularly in tumor imaging. This review emphasizes the role of CDs in the domain of PAI, highlighting their characteristics like biocompatibility, enhanced spatial resolution, optical absorption in the NIR region, and facile surface functionalization for tumor‐ targeted imaging. The study explores the use of CDs for enhancing spatial resolution in PAI for improved detection and visualization of tumors in organs such as the breast, cervical, liver, gastrointestinal, skin, cardiovascular system, nervous system, and others. Challenges associated with PAI, such as optimizing the signal‐to‐noise ratio and ensuring stability under physiological conditions, have also been discussed.

IFGAN: Pre- to Post-Contrast Medical Image Synthesis Based on Interactive Frequency GAN

Medical images provide a visual representation of the internal structure of the human body. Injecting a contrast agent can increase the contrast of diseased tissues and assist in the accurate identification and assessment of conditions. Considering the adverse reactions and side effects caused by contrast agents, previous methods synthesized post-contrast images with pre-contrast images to bypass the administration process. However, existing methods pay inadequate attention to reasonable mapping of the lesion area and ignore gaps between post-contrast and real images in the frequency domain. Thus, in this paper, we propose an interactive frequency generative adversarial network (IFGAN) to solve the above problems and synthesize post-contrast images from pre-contrast images. We first designed an enhanced interaction module that is embedded in the generator to focus on the contrast enhancement region. Within it, target and reconstruction branch features interact to control the local contrast enhancement region feature and maintain the anatomical structure. We propose focal frequency loss to ensure the consistency of post-contrast and real images in the frequency domain. The experimental results demonstrated that IFGAN outperforms other sophisticated approaches in terms of preserving the accurate contrast enhancement of lesion regions and anatomical structures. Specifically, our method produces substantial improvements of 7.9% in structural similarity (SSIM), 36.3% in the peak signal-to-noise ratio (PSNR), and 8.5% in multiscale structural similarity (MSIM) compared with recent state-of-the-art methods.

In situ isotropic 3D imaging of vasculature perfusion specimens using x-ray microscopic dual-energy CT.

Ex vivo x-ray angiography provides high-resolution, three-dimensional information on vascular phenotypes down to the level of capillaries. Sample preparation for ex vivo angiography starts with the removal of blood from the vascular system, followed by perfusion with an x-ray dense contrast agent mixed with a carrier such as gelatine or a polymer. Subsequently, the vascular micro-architecture of harvested organs is imaged in the intact fixed organ. In the present study, we present novel microscopic dual-energy CT (microDECT) imaging protocols that allow to visualise and analyse microvasculature in situ with reference to the morphology of hard and soft tissue. We show that the spectral contrast of µAngiofil and Micropaque barium sulphate in perfused specimens allows for the effective separation of vasculature from mineralised skeletal tissues. Furthermore, we demonstrate the counterstaining of perfused specimens using established x-ray dense contrast agents to depict blood vessels together with the morphology of soft tissue. Phosphotungstic acid (PTA) is used as a counterstain that shows excellent spectral contrast in both µAngiofil and Micropaque barium sulphate-perfused specimens. A novel Sorensen-buffered PTA protocol is introduced as a counterstain for µAngiofil specimens, as the polyurethane polymer is susceptible to artefacts when using conventional staining solutions. Finally, we demonstrate that counterstained samples can be automatically processed into three separate image channels (skeletal tissue, vasculature and stained soft tissue), which offers multiple new options for data analysis. The presented microDECT workflows are suited as tools to screen and quantify microvasculature and can be implemented in various correlative imaging pipelines to target regions of interest for downstream light microscopic investigation.

Improved visualisation of ACP-engineered osteoblastic spheroids: a comparative study of contrast-enhanced micro-CT and traditional imaging techniques

This study investigates osteoblastic cell spheroid cultivation methods, exploring flat-bottom, U-bottom, and rotary flask techniques with and without amorphous calcium phosphate (ACP) supplementation to replicate the 3D bone tissue microenvironment. ACP particles derived from eggshell waste exhibit enhanced osteogenic activity in 3D models. However, representative imaging of intricate 3D tissue-engineered constructs poses challenges in conventional imaging techniques due to notable scattering and absorption effects in light microscopy, and hence limited penetration depth. We investigated contrast-enhanced micro-CT as a methodological approach for comprehensive morphological 3D-analysis of thein-vitromodel and compared the technique with confocal laser scanning microscopy, scanning electron microscopy and classical histology. Phosphotungstic acid and iodine-based contrast agents were employed for micro-CT imaging in laboratory and synchrotron micro-CT imaging. Results revealed spheroid shape variations and structural integrity influenced by cultivation methods and ACP particles. The study underscores the advantage of 3D spheroid models over traditional 2D cultures in mimicking bone tissue architecture and cellular interactions, emphasising the growing demand for novel imaging techniques to visualise 3D tissue-engineered models. Contrast-enhanced micro-CT emerges as a promising non-invasive imaging method for tissue-engineered constructs containing ACP particles, offering insights into sample morphology, enabling virtual histology before further analysis.

Micro-CT study of human laryngeal structures using phosphotungstic agent staining.

Traditional dissection methods are primarily limited by challenges in identifying minute structures, which can lead to irreversible tissue damage. Anatomical observation of the larynx is particularly challenging in educational and clinical settings owing to its microscopic structures and complex three-dimensional (3D) nature, making it difficult to dissect. Therefore, this study aimed to demonstrate that micro-computed tomography (micro-CT) imaging of the larynx can serve as an effective alternative for educational and clinical purposes, overcoming these limitations. Three laryngeal specimens were obtained from cadavers, stained with a phosphotungstic acid-based contrast agent, and imaged using enhanced micro-CT. The resulting images were reconstructed in three dimensions, allowing for a detailed 3D observation of the specimens. Phosphotungstic contrast-enhanced micro-CT provided comprehensive anatomical information on laryngeal structures, including muscles, nerves, arteries, and vocal folds. This study demonstrates the high effectiveness of micro-CT in producing detailed structural images of the larynx, enabling 3D observation of even the smallest anatomical structures. These images can be applied in both educational and clinical settings to analyze the human larynx, effectively overcoming the limitations of traditional dissection methods. This approach facilitates the analysis of laryngeal structures that are otherwise difficult to observe with the naked eye.

Can the second phase of contrast-enhanced MRA of the neck provide additional information in the acute stroke setting?

Double-concentration magnetic resonance imaging (MRI) contrast agents are frequently used in contrast-enhanced MR angiography (CE-MRA) of the head and neck. To avoid mistiming the peak concentration of intraluminal contrast (due to shorter duration of peak), a second acquisition is sometimes performed. To evaluate additional information from the second acquisition of CE-MRA and compare the collateral scoring to the hypoperfusion index obtained on MR perfusion, and to investigate presence of pseudo-occlusion using the second phase of CE-MRA. A retrospective study was conducted. CE-MRA of the brain/neck, dynamic susceptibility contrast (DSC) MR perfusion scan (in majority) and subsequent digital subtraction angiography (DSA) were evaluated in patients with previous acute internal carotid artery (ICA)/middle cerebral artery (MCA) occlusion. Evaluation of CE-MRA/MR perfusion and DSA was performed by three experienced neuroradiologists and one neurointerventionist, respectively. The site of ICA occlusion was seen to be distal to the site noted on early arterial phase (pseudo-occlusion of ICA) in 28.5% of patients. A significant negative correlation was seen between a higher HIR and collateral score. Evaluation of second phase CE-MRA can provide valuable information that may be otherwise lost if only the early arterial phase is evaluated.

Development and validation of a controlled heating apparatus for long‐term MRI of 3D microfluidic tumor models

AbstractConventional testing of novel contrast agents for magnetic resonance imaging (MRI) involves cell and animal studies. However, 2D cultures lack dynamic flow and in vivo MRI is limited by regulatory approval of long‐term anesthesia use. Microfluidic tumor models (MTMs) offer a cost‐effective, reproducible, and high throughput platform for bridging cell and animal models. Yet, MRI of microfluidic devices is challenging, due to small fluid volumes generating low sensitivity. For the first time, an MRI of MTMs was performed at low field strength (1 T) using conventional imaging equipment without microcoils. To enable longitudinal MRI, we developed (1) CHAMP‐3 (controlled heating apparatus for microfluidics and portability) which heats MTMs during MRI scans and (2) an MRI‐compatible temperature monitoring system. CHAMP‐3 maintained chip surface temperature at ~37°C and the media inside at ~35.5°C. Enhanced T1‐weighted MRI contrast was achieved in 3D MTMs with free manganese (Mn2+) solutions and Mn2+ labeled tumor cells.

Magnitude and timescales of Ca isotope variability in human urine: implications for bone mass balance monitoring.

Calcium (Ca) isotopes in blood/urine are emerging biomarkers of bone mineral balance (BMB) in the human body. While multiple studies have investigated Ca isotopes in patients suffering from diseases affecting BMB, comparatively little effort has been devoted to understanding the homeostasis of Ca isotopes in healthy individuals. Here, we report on a longitudinal study of the urine Ca isotope composition (δ44/42CaUrine) from 22 healthy participants (age 19 to 60) over timescales ranging from days to months. Data from a single participant collected over a 30-day period show that morning urine is an excellent proxy for 24 hr pooled urine fractions. Data from all participants reveal large inter-individual variability in δ44/42CaUrine (up to 2.2 ‰), which is partly due to anthropometric differences, as shown by a correlation between the participants' body mass index (BMI) and δ44/42CaUrine values. In contrast, intra-individual data reveal encouraging stability (within ∼ ±0.2-0.3 ‰) over timescales>160 days, indicating that self-referencing approaches for BMB monitoring hold greater promise than cross sectional ones. Our data confirm that intra-individual δ44/42CaUrine variations are mainly a function of Ca reabsorption in the kidney, but also reveal the impact of other (and at times equally important) drivers, such as diet, alcohol consumption, physical exercise, or fasting. We also find that a magnetic resonance imaging contrast agent (gadolinium) can lead to artifacts during Ca isotope analysis. Based on our results, a series of practical considerations for the use of Ca isotopes in urine as tracers of BMB is presented.

Dynamic glucose-enhanced MRI of gliomas: A preliminary clinical application.

The study aimed to investigate the feasibility of dynamic glucose-enhanced (DGE) MRI technology in the clinical application of glioma. Twenty patients with glioma were examined using a preoperative DGE-MRI protocol before clinical intervention. A brief hyperglycemic state was achieved by injecting 50 mL of 50% w/w D-glucose intravenously during the DGE imaging. The total acquisition time for the DGE was 15 min. Area-under-the-curve (AUC) images were calculated using the DGE images. AUC2-7min values of the glioma core, margin area, edema area, and contralateral brain parenchyma were compared using Mann-Whitney U tests. Overall, gray and white matter areas in the AUC images showed relatively low DGE signal change and bilateral symmetry. However, the tumor cores displayed a significant hyperintensity. A high DGE signal change was also seen in the necrotic, cystic, and cerebrospinal areas. These results show that DGE MRI is a feasible technique for the study of brain tumors as part of a clinical exam. Importantly, DGE MRI showed enhancement in areas confirmed histopathologically as tumors, whereas Gd T1w MRI did not show any enhancement in this area. Since the D-glucose molecule is smaller than Gd-based contrast agents, DGE MRI may be more sensitive to subtle blood-brain barrier disruptions, thus potentially providing early information about possible malignancy. These findings provide a new perspective for the further exploration and analysis of D-glucose uptake in brain tumors.

Effect of Microbubble Size, Composition, and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening.

Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubbles (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model. Using MRI-guided MB + FUS, we targeted the striatum and assessed extravasation of an MRI contrast agent to assess BBBO and RNaseq to assess SIR. Our results revealed distinct effects of these parameters on BBBO and SIR. Specifically, at a matched microbubble volume dose (MVD), MB size did not affect the extent of BBBO, but smaller (1 μm diameter) MBs exhibited a lower classification of SIR than larger (3 or 5 μm diameter) MBs. Lipid-shelled microbubbles exhibited greater BBBO and a more pronounced SIR compared to albumin-shelled microbubbles, likely owing to the latter's poor in vivo stability. As expected, increasing the number of sonication points resulted in greater BBBO and SIR. Furthermore, correlation analysis revealed strong associations between passive cavitation detection measurements of harmonic and inertial MB echoes, BBBO, and the expression of SIR gene sets. Our findings highlight the critical role of MB and FUS parameters in modulating BBBO and subsequent SIR in the brain. These insights inform the development of targeted drug delivery strategies and the mitigation of adverse inflammatory reactions in neurological disorders.