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Background & Aims: Non-invasive scores have been proposed to identify patients with fibrotic, metabolic dysfunction-associated steatohepatitis (MASH), who are at the highest risk of progression to complications of cirrhosis and may benefit from pharmacologic treatments. However, data in patients with type 2 diabetes (T2DM) are lacking. The aim of this multicenter prospective study was to perform a head-to-head comparison of FAST (FibroScan-aspartate aminotransferase [AST]), MAST (MRI-AST), MEFIB (magnetic resonance elastography [MRE] plus FIB-4), and FNI (fibrotic NASH index) for detecting fibrotic MASH in patients with T2DM., Methods: A total of 330 outpatients with T2DM and biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) from the QUID-NASH study (NCT03634098), who underwent FibroScan, MRI-proton density fat fraction and MRE at the time of liver biopsy were studied. The main outcome was fibrotic MASH, defined as NAS ≥4 (with at least one point for each parameter) and fibrosis stage ≥2 (centrally reviewed)., Results: All data for score comparisons were available for 245 patients (median age 59 years, 65% male, median BMI 31 kg/m 2 ; fibrotic MASH in 39%). FAST and MAST had similar accuracy (AUROCs 0.81 vs. 0.79, p = 0.41) but outperformed FNI (0.74; p = 0.01) and MEFIB (0.68; p <0.0001). When using original cut-offs, MAST outperformed FAST, MEFIB and FNI when comparing the percentage of correctly classified patients, in whom liver biopsy would be avoided (69% vs. 48%, 46%, 39%, respectively; p <0.001). When using cut-offs specific to our population, FAST outperformed FNI and MAST (56% vs. 40%, and 38%, respectively; p <0.001)., Conclusion: Our findings show that FAST, MAST, MEFIB and FNI are accurate non-invasive tools to identify patients with T2DM and fibrotic MASH in secondary/tertiary diabetes clinics. Cut-offs adapted to the T2DM population should be considered., Impact and Implications: Among patients with type 2 diabetes (T2DM), identifying those with metabolic dysfunction-associated steatohepatitis and significant fibrosis, who are the most at risk of developing clinical liver-related outcomes and who may benefit from pharmacologic treatments, is an unmet need. In this prospective multicenter study, we compared four non-invasive scores, three based on imaging (MRI or ultrasound technologies) and one on laboratory blood tests, for this purpose, using original and study-specific cut-offs. Our findings show that FAST, MAST, MEFIB and FNI are accurate non-invasive tools to identify patients with T2DM and fibrotic MASH in secondary/tertiary diabetes clinics. Cut-offs adapted to the T2DM population should be considered., Trial Registration Number: NCT03634098., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Similarly to the controlled attenuation parameter (CAP), the ultrasound-based attenuation imaging (ATI) can quantify hepatic steatosis. We prospectively compared the performance of ATI and CAP for the diagnosis of hepatic steatosis in patients with type 2 diabetes and nonalcoholic fatty liver disease using histology and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) as references., Methods: Patients underwent ATI and CAP measurement, MRI, and biopsy on the same day. Steatosis was classified as S0, S1, S2, and S3 on histology (<5%, 5%-33%, 33%-66%, and >66%, respectively) while the thresholds of 6.4%, 17.4%, and 22.1%, respectively, were used for MRI-PDFF. The area under the curve (AUC) of ATI and CAP was compared using a DeLong test., Results: Steatosis could be evaluated in 191 and 187 patients with MRI-PDFF and liver biopsy, respectively. For MRI-PDFF steatosis, the AUC of ATI and CAP were 0.86 (95% confidence interval [CI], 0.81-0.91) vs 0.69 (95% CI, 0.62-0.75) for S0 vs S1-S3 (P = .02) and 0.71 (95% CI, 0.64-0.77) vs 0.69 (95% CI, 0.61-0.75) for S0-S1 vs S2-S3 (P = .60), respectively. For histological steatosis, the AUC of ATI and CAP were 0.92 (95% CI, 0.87-0.95) vs 0.95 (95% CI, 0.91-0.98) for S0 vs S1-S3 (P = .64) and 0.79 (95% CI, 0.72-0.84) vs 0.76 (95% CI, 0.69-0.82) for S0-S1 vs S2-S3 (P = .61), respectively., Conclusion: ATI may be used as an alternative to CAP for the diagnosis and quantification of steatosis, in patients with type 2 diabetes and nonalcoholic fatty liver disease., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In the framework of algebraic inversion, magnetic resonance elastography (MRE) repeatability, reproducibility and robustness were evaluated on extracted shear velocities (or elastic moduli). The same excitation system was implemented at two sites equipped with clinical MR scanners of 1.5 and 3 T. A set of four elastic, isotropic, homogeneous calibrated phantoms of distinct elasticity representing the spectrum of liver fibrosis severity was mechanically characterized. The repeatability of the measurements and the reproducibility between the two platforms were found to be excellent with mean coefficients of variations of 1.62% for the shear velocity mean values and 1.95% for the associated standard deviations. MRE velocities were robust to the amplitude and pattern variations of the displacement field with virtually no difference between outcomes from both magnets at identical excitation frequencies, even when the displacement field amplitude was six times smaller. However, MRE outcomes were very sensitive to the number of voxels per wavelength, s, of the recorded displacement field, with relative biases reaching 62% and precision loss by a factor of up to 23.5. For both magnetic field strengths, MRE accuracy and precision were largely degraded outside of established conditions of validity (6 ≲ s ≲ 9), resulting in estimated shear velocity values not significantly different between phantoms of increasing elasticity. When fulfilling the spatial sampling conditions, either prospectively in the acquisition or retrospectively before the reconstruction, MRE produced quantitative measurements that allowed to unambiguously discriminate, with infinitesimal p values, between the phantoms mimicking increasing severity of liver fibrosis., (© 2021 John Wiley & Sons, Ltd.)

The water proton longitudinal relaxation time, T 1 , is a common and useful MR parameter in nephrology research. Here we provide three step-by-step T 1 -mapping protocols suitable for different types of nephrology research. Firstly, we provide a single-slice 2D saturation recovery protocol suitable for studies of global pathology, where whole-kidney coverage is unnecessary. Secondly, we provide an inversion recovery type imaging protocol that may be optimized for specific kidney disease applications. Finally, we also provide imaging protocol for small animal kidney imaging in a clinical scanner.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

In renal MRI, measurement of the T 1 relaxation time of water molecules may provide a valuable biomarker for a variety of pathological conditions. Due to its sensitivity to the tissue microenvironment, T 1 has gained substantial interest for noninvasive imaging of renal pathology, including inflammation and fibrosis. In this chapter, we will discuss the basic concept of T 1 mapping and different T 1 measurement techniques and we will provide an overview of emerging preclinical applications of T 1 for imaging of kidney disease.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

The computation of T 1 maps from MR datasets represents an important step toward the precise characterization of kidney disease models in small animals. Here the main strategies to analyze renal T 1 mapping datasets derived from small rodents are presented. Suggestions are provided with respect to essential software requirements, and advice is provided as to how dataset completeness and quality may be evaluated. The various fitting models applicable to T 1 mapping are presented and discussed. Finally, some methods are proposed for validating the obtained results.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

Background: Malignant tumors are associated with increased tissue rigidity, which can be an indicator of tumor progression. MR elastography (MRE) has the potential to study the variations of tumor mechanical properties. ex vivo studies have shown the ability of MRE to assess increase of mechanical properties; nevertheless, it has not yet been observed in vivo., Purpose: To propose a method to assess the increase in mechanical properties of tumors in vivo under static external compression using MRE., Study Type: Prospective, experimental study., Animal Model: Forty-six SCID mice with subcutaneous tumor implantation (patient-derived hepatocellular carcinoma xenografts, Model 1, n = 13, and Model 2, n = 33)., Field Strength/sequence: 7.0T; a spin echo sequence was used for anatomical images and a modified spin echo sequence for elastography acquisitions with a vibration frequency of 600 Hz., Assessment: An inflatable balloon was placed on the abdomen to apply a load to the tumor. MRE acquisitions were performed at the basal state and at increasing compression levels. Anatomical images were used to calculate the octahedral shear strain between the tumor at the basal strain state and each strain level. For six mice (Model 2), each static preloading scan was acquired twice consecutively without moving the mouse to evaluate repeatability. Statistical Tests: The Bland-Altman method was used to assess repeatability. Correlations between tumor stiffness and deformation were evaluated with Pearson correlation coefficients., Results: For stiffness (G*), a good repeatability was obtained between the acquisitions; the limits of agreement of the Bland-Altman test were [-10.17%; 11.49%] with an absolute bias of 0.66%. A significant correlation between tumor stiffness and deformation was observed for both models (Model 1: r = 0.57, P < 0.0001 and Model 2: r = 0.31, P < 0.0001)., Data Conclusion: We establish that tumor mechanical properties can increase under mechanical compression. This increase can effectively be monitored using a proposed MRE setup., Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1982-1989., (© 2019 International Society for Magnetic Resonance in Medicine.)

Background: Inflammation involves a heterogeneous macrophage population, for which there is no readily available MR assessment method., Purpose: To assess the feasibility of distinguishing proinflammatory M1 and antiinflammatory M2 macrophages at MRI enhanced with gadolinium liposomes or ultrasmall superparamagnetic iron oxide particles., Study Type: In vitro., Specimen: We employed cultured RAW macrophages. M0 macrophages were polarized with lipopolysaccharide (LPS) or interleukin-4 (IL-4), resulting in M1 or M2 macrophages. The macrophages were incubated with gadolinium (±rhodamine) liposomes or iron oxide particles and cell pellets were prepared for MRI., Field Strength/sequence: Transverse relaxation rates and quantitative susceptibility were obtained at 3.0T with multiecho turbo spin echo and spoiled gradient echo sequences., Assessment: MRI results were compared with confocal microscopy, flow cytometry, and expression of endocytosis, M1 and M2 genes., Statistical Tests: Mann-Whitney and Kruskal-Wallis tests were performed., Results: Higher transverse relaxation rates and susceptibility were observed in M1 than in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO) and significantly different susceptibility in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO). These MRI results were confirmed at confocal microscopy and flow cytometry. LPS macrophages displayed M1 gene expression, whereas IL-4 macrophages showed M2 polarization and lower endocytosis gene expression rates., Data Conclusion: These in vitro results show that it is feasible to distinguish between proinflammatory M1 and antiinflammatory M2 macrophages according to their level of contrast agent uptake at MRI., Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1166-1173., (© 2018 International Society for Magnetic Resonance in Medicine.)

The viscoelastic properties of the liver and spleen can be assessed with magnetic resonance elastography (MRE). Several actuators, MRI acquisition sequences and reconstruction algorithms have been proposed for this purpose. Reproducible results are obtained, especially when the examination is performed in standard conditions with the patient fasting. Accurate staging of liver fibrosis can be obtained by measuring liver stiffness or elasticity with MRE. Moreover, emerging evidence shows that assessing the tissue viscous parameters with MRE is useful for characterizing liver inflammation, non-alcoholic steatohepatitis, hepatic congestion, portal hypertension, and hepatic tumors. Further advances such as multifrequency acquisitions and compression-sensitive MRE may provide novel quantitative markers of hepatic and splenic mechanical properties that may improve the diagnosis of hepatic and splenic diseases., (Copyright © 2018 John Wiley & Sons, Ltd.)

Murine radiation-induced rectocolitis is considered to be a relevant animal model of gastrointestinal inflammation. The purpose of our study was to compare quantitative MRI and histopathological features in this gastrointestinal inflammation model. Radiation rectocolitis was induced by localized single-dose radiation (27 Gy) in Sprague-Dawley rats. T 2 -weighted, T 1 -weighted and diffusion-weighted MRI was performed at 7 T in 16 rats between 2 and 4 weeks after irradiation and in 10 control rats. Rats were sacrificed and the histopathological inflammation score of the colorectal samples was assessed. The irradiated rats showed significant increase in colorectal wall thickness (2.1 ± 0.3 mm versus 0.8 ± 0.3 mm in control rats, P < 0.0001), normalized T 2 signal intensity (4 ± 0.8 versus 2 ± 0.4 AU, P < 0.0001), normalized T 1 signal intensity (1.4 ± 0.1 versus 1.1 ± 0.2 AU, P = 0.0009) and apparent and pure diffusion coefficients (ADC and D) (2.06 × 10 -3 ± 0.34 versus 1.51 × 10 -3 ± 0.23 mm 2 /s, P = 0.0004, and 1.97 × 10 -3 ± 0.43 mm 2 /s versus 1.48 × 10 -3 ± 0.29 mm 2 /s, P = 0.008, respectively). Colorectal wall thickness (r = 0.84, P < 0.0001), normalized T 2 signal intensity (r = 0.85, P < 0.0001) and ADC (r = 0.80, P < 0.0001) were strongly correlated with the histopathological inflammation score, whereas normalized T 1 signal intensity and D were moderately correlated (r = 0.64, P = 0.0006, and r = 0.65, P = 0.0003, respectively). High-field MRI features of single-dose radiation-induced rectocolitis in rats differ significantly from those of control rats. Quantitative MRI characteristics, especially wall thickness, normalized T 2 signal intensity, ADC and D, are potential markers of the histopathological inflammation score., (Copyright © 2018 John Wiley & Sons, Ltd.)

Purpose To determine the relationship of liver fibrosis, inflammation, and steatosis with the magnetic resonance (MR) viscoelastic and diffusion parameters in patients with chronic liver disease and to compare the diagnostic accuracy of the imaging parameters in staging liver fibrosis. Materials and Methods Consecutive patients with chronic liver disease scheduled for liver biopsy were prospectively recruited from November 2010 to October 2012 for this institutional review board-approved study after they provided written informed consent. Sixty-eight patients underwent three-dimensional MR elastography and intravoxel incoherent motion diffusion-weighted MR imaging with a 1.5-T MR system. Fibrosis, inflammation, and steatosis were assessed with the METAVIR and steatosis, activity, and fibrosis (or SAF) scoring systems. Spearman correlation and multiple regression analyses were performed to determine the relationship between liver fibrosis, inflammation, steatosis, and alanine aminotransferase (ALT) levels and viscoelastic and diffusion parameters. The accuracy of three-dimensional MR elastography and diffusion-weighted MR imaging in the determination of fibrosis stage was assessed with Obuchowski measures. Results At multiple regression analysis, fibrosis was the only variable associated with viscoelastic parameters (β = 0.6, P < .001, R 2 = 0.33 for shear modulus; β = 0.6, P < .001, R 2 = 0.32 for elasticity). Fibrosis had a weaker independent association with the apparent diffusion coefficient (β = -0.3, P = .02, R 2 = 0.33) than did steatosis (β = -0.5, P < .001, R 2 = 0.33). Steatosis was the only factor independently associated with the pure diffusion coefficient (β = -0.4, P = .002, R 2 = 0.22). Inflammation and ALT level were not associated with the viscoelastic or diffusion parameters. The diagnostic accuracy of fibrosis staging was significantly higher when measuring the shear modulus rather than the apparent diffusion coefficient (Obuchowski measures, 0.82 ± 0.04 vs 0.30 ± 0.06; P < .001). Conclusion Fibrosis is independently associated with the MR viscoelastic parameters and is less associated with the diffusion parameters than is steatosis. These results and those of diagnostic accuracy suggest that MR elastography should be preferred over diffusion-weighted MR imaging in the staging of liver fibrosis. © RSNA, 2016.

Our aim is to develop a clinically viable, fast-acquisition, prostate MR elastography (MRE) system with transperineal excitation. We developed a new actively shielded electromagnetic transducer, designed to enable quick deployment and positioning within the scanner. The shielding of the transducer was optimized using simulations. We also employed a new rapid pulse sequence that encodes the three-dimensional displacement field in the prostate gland using a fractionally encoded steady-state gradient echo sequence, thereby shortening the acquisition time to a clinically acceptable 8-10 min. The methods were tested in two phantoms and seven human subjects (six volunteers and one patient with prostate cancer). The MRE acquisition time for 24 slices, with an isotropic resolution of 2 mm and eight phase offsets, was 8 min, and the total scan, including positioning and set-up, was performed in 15-20 min. The phantom study demonstrated that the transducer does not interfere with the acquisition process and that it generates displacement amplitudes that exceed 100 µm even at frequencies as high as 300 Hz. In the in vivo human study, average wave amplitudes of 30 µm (46 µm at the apex) were routinely achieved within the prostate gland at 70 Hz. No pain or discomfort was reported. Results in a single patient suggest that MRE can identify cancer tumors, although this result is preliminary. The proposed methods allow the integration of prostate MRE with other multiparametric MRI methods. The results of this study clearly motivate the clinical evaluation of transperineal MRE in patients., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objective: To assess the value of the liver and spleen viscoelastic parameters at multifrequency MR elastography to determine the degree of portal hypertension and presence of high-risk oesophageal varices in patients with cirrhosis., Methods: From January to September 2012, 36 consecutive patients with cirrhosis evaluated for transplantation were prospectively included. All patients underwent hepatic venous pressure gradient (HVPG) measurements and endoscopy to assess oesophageal varices. Multifrequency MR elastography was performed within the liver and spleen. The shear, storage and loss moduli were calculated and compared to the HVPG with Spearman coefficients and multiple regressions. Patients with and without severe portal hypertension and high-risk varices were compared with Mann-Whitney tests, logistic regression and ROC analysis., Results: The liver storage and loss moduli and the spleen shear, storage and loss moduli correlated with the HVPG. At multiple regression, only the liver and the spleen loss modulus correlated with the HVPG (r = 0.44, p = 0.017, and r = 0.57, p = 0.002, respectively). The spleen loss modulus was the best parameter for identifying patients with severe portal hypertension (p = 0.019, AUROC = 0.81) or high-risk varices (p = 0.042, AUROC = 0.93)., Conclusions: The spleen loss modulus appears to be the best parameter for identifying patients with severe portal hypertension or high-risk varices., Key Points: 1. Noninvasive HVPG assessment can be performed with liver and spleen MR elastography 2. The spleen loss modulus enables the detection of high-risk oesophageal varices 3. The spleen loss modulus enables the detection of severe portal hypertension.

Liver perfusion imaging is a quantitative functional investigation. Liver perfusion imaging is complicated because of the liver's dual vascular supply, artefacts due to respiratory movements and the fenestrated sinusoidal capillaries which allow the contrast medium to diffuse out. Liver perfusion can be examined by ultrasound, CT or MRI: each technique has its limitations and specific features. The major indications in hepatology are oncology (detection, characterization and tumor response) and non-invasive investigation of patients with chronic liver disease. Work is needed to standardize acquisition and modeling methods to allow wider use of results and more widespread use of the technique., (Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Objective: To use an automated water-suppressed magnetic resonance imaging (MRI) method to objectively assess adipose tissue (AT) volumes in whole body and specific regional body components (subcutaneous, thoracic and peritoneal) of obese and lean mice., Materials/methods: Water-suppressed MR images were obtained on a 7T, horizontal-bore MRI system in whole bodies (excluding head) of 26 week old male C57BL6J mice fed a control (10% kcal fat) or high-fat diet (60% kcal fat) for 20 weeks. Manual (outlined regions) versus automated (Gaussian fitting applied to threshold-weighted images) segmentation procedures were compared for whole body AT and regional AT volumes (i.e., subcutaneous, thoracic, and peritoneal). The AT automated segmentation method was compared to dual-energy X-ray (DXA) analysis., Results: The average AT volumes for whole body and individual compartments correlated well between the manual outlining and the automated methods (R2>0.77, p<0.05). Subcutaneous, peritoneal, and total body AT volumes were increased 2-3 fold and thoracic AT volume increased more than 5-fold in diet-induced obese mice versus controls (p<0.05). MRI and DXA-based method comparisons were highly correlative (R2=0.94, p<0.0001)., Conclusions: Automated AT segmentation of water-suppressed MRI data using a global Gaussian filtering algorithm resulted in a fairly accurate assessment of total and regional AT volumes in a pre-clinical mouse model of obesity., (© 2013 Elsevier Inc. All rights reserved.)

Purpose: The purpose was to describe the design and fabrication of a driver suitable for magnetic resonance elastography (MRE) of the head and neck and to assess its performance in evaluating human parotid gland, lymph nodes and thyroid at 3.0 T., Materials and Methods: A head and neck driver was fabricated using a commercial transducer, headrest mould and piston extension. Driver performance was tested using a motion-sensitized spin-echo MRE pulse sequence. Six healthy volunteers and three patients (two metastatic nodes and one papillary carcinoma) were evaluated using MRE. Viscoelastic maps were computed to obtain storage modulus (G') and loss modulus (G") of the normal parotid and thyroid, metastatic node and thyroid cancer. Reproducibility was assessed by coefficient of variation., Results: All subjects completed MRE examination without discomfort. Initial G' and G" values were as follows: normal parotid gland, 1.12 kPa and 0.48 kPa; thyroid, 0.58 kPa and 0.42 kPa; metastatic node, 0.66 kPa and 0.58 kPa; and thyroid cancer, 0.17 kPa and 0.28 kPa. Based on parotid data, the coefficient of variation for G' and G" was 4.7% and 9.8%., Conclusion: A new MRE driver for head and neck was successfully implemented, and our initial results suggested the device was suitable for the mechanical assessment of tissues in the head and neck., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To assess the value of the viscoelastic parameters in the characterisation of liver tumours at MR elastography., Patients and Methods: Ninety-four patients with liver tumours >1 cm prospectively underwent MR elastography using 50-Hz mechanical waves and a full three-directional motion-sensitive sequence. The model-free viscoelastic parameters (the complex shear modulus and its real and imaginary parts, i.e. the storage and loss moduli) were calculated in 72 lesions after exclusion of cystic, treated or histopathologically undetermined tumours., Results: We observed higher absolute shear modulus and loss modulus in malignant versus benign tumours (3.38 ± 0.26 versus 2.41 ± 0.15 kPa, P < 0.01 and 2.25 ± 0.26 versus 1.05 ± 0.13 kPa, P < 0.001, respectively). Moreover, the loss modulus of hepatocellular carcinomas was significantly higher than in benign hepatocellular tumours. The storage modulus did not differ significantly between malignant and benign tumours. The area under the receiver-operating characteristic curve of loss modulus was significantly larger than that of the absolute shear modulus and storage modulus when comparing malignant and benign lesions., Conclusions: The increased loss modulus is a better discriminator between benign and malignant tumours than the increased storage modulus or absolute value of the shear modulus., Key Points: • Magnetic Resonance elastography is a new method of assessing the liver. • Increased loss modulus is an indicator of malignancy in hepatic tumours. • Loss modulus is a better discriminator than absolute shear modulus values. • The viscoelastic properties of lesions offer promise for characterising liver tumours.

Laser immunotherapy (LIT) uses a synergistic approach to treat cancer systemically through local laser irradiation and immunological stimulation. Currently, LIT utilizes dye-assisted noninvasive laser irradiation to achieve selective photothermal interaction. However, LIT faces difficulties treating deeper tumors or tumors with heavily pigmented overlying skin. To circumvent these barriers, we use interstitial laser irradiation to induce the desired photothermal effects. The purpose of this study is to analyze the thermal effects of interstitial irradiation using proton resonance frequency (PRF). An 805-nm near-infrared laser with an interstitial cylindrical diffuser was used to treat rat mammary tumors. Different power settings (1.0, 1.25, and 1.5 W) were applied with an irradiation duration of 10 min. The temperature distributions of the treated tumors were measured by a 7 T magnetic resonance imager using PRF. We found that temperature distributions in tissue depended on both laser power and time settings, and that variance in tissue composition has a major influence in temperature elevation. The temperature elevations measured during interstitial laser irradiation by PRF and thermocouple were consistent, with some variations due to tissue composition and the positioning of the thermocouple's needle probes. Our results indicated that, for a tissue irradiation of 10 min, the elevation of rat tumor temperature ranged from 8 to 11°C for 1 W and 8 to 15°C for 1.5 W. This is the first time a 7 T magnetic resonance imager has been used to monitor interstitial laser irradiation via PRF. Our work provides a basic understanding of the photothermal interaction needed to control the thermal damage inside a tumor using interstitial laser treatment. Our work may lead to an optimal protocol for future cancer treatment using interstitial phototherapy in conjunction with immunotherapy.

Purpose: To demonstrate that OKN007, a disulfonyl derivative of phenyl-tert-butyl nitrone (PBN), has anti-glioma activity in the clinically relevant C6 rat glioma model using multi-parametric magnetic resonance imaging., Materials and Methods: Twenty-one rats were intracerebrally implanted with C6 cells and administered OKN007 or kept as controls. Animals were monitored with MRI at 7 Tesla (T), using morphologic, diffusion-weighted and perfusion imaging, followed by histology and Western blots of angiogenesis and inflammatory markers., Results: OKN007 was found to decrease tumor volumes and increase survival. The glioma tissues of OKN007-treated rats were found to have longitudinal apparent diffusion coefficients (ADC(z)) of 0.76 +/- 0.06 x 10(-3) mm(2)/s, similar to the contralateral tissue and significantly smaller than untreated gliomas (0.97 +/- 0.13 x 10(-3) mm(2)/s). They had higher perfusion rates (66 +/- 4 mL/100 g.min) than untreated gliomas (26 +/- 7 mL/100 g.min). All examined molecular markers were decreased in OKN007-treated rat gliomas, compared with elevated levels in untreated rats., Conclusion: MRI assessment was successfully used to monitor a decrease in tumor growth, and corresponding alterations in ADC and perfusion rates in rat C6 gliomas treated with the anti-glioma agent, OKN007., ((c) 2010 Wiley-Liss, Inc.)

Abstract: With increasing age, a subset of otherwise healthy individuals undergoes impairments in learning and memory that have been termed mild cognitive impairment (MCI). The enhanced neuronal activity associated with learning and memory requires increased cerebral blood flow (CBF) to specific brain regions. However, the interactions between cerebral blood flow and MCI remain unclear. In this study, we address whether baseline or hypercapnia-induced (increased blood CO2 levels) changes in CBF are modified with age, and whether these measures are predictive of cognitive status in rodents. Adult and aged rats were evaluated using a hippocampally-dependent task in a water maze. Aged rats were classified as memory-impaired or memory-intact based on performance comparisons with adult rats. Cerebral blood flow was assessed using flow-alternating inversion recovery (FAIR) magnetic resonance imaging (MRI), before and after breathing 10% CO2. The transition period between CO2 concentrations was examined with blood oxygen level dependent (BOLD) MRI. Separation of aged animals into memory-intact and impaired categories revealed increased basal perfusion in the dorsal hippocampus of memory-impaired versus memory-intact aged animals. Linear regression revealed that higher hippocampal perfusion was correlated with impaired memory in aged animals, and a logistic regression indicated that hippocampal perfusion predicted spatial memory ability. Several brain regions of aged rats demonstrated an attenuation of the perfusion increase normally observed in adult rats under hypercapnia. Memory-impaired animals were the primary contributor to this effect, as their perfusion response to hypercapnia was significantly reduced compared to adult animals. Aged, memory-intact animals were not significantly different from adults. BOLD MRI demonstrated a reduced response in aged animals to hypercapnia, with impaired animals being the primary contributor to the effect. A logistic regression model based on basal and hypercapnia perfusion correctly predicted cognitive status in 83.3% of animals tested. Our results indicate that age-related changes in vascular reactivity and perfusion are important contributing factors in memory impairment. [Copyright &y& Elsevier]

The tyrosine kinase receptor, c-Met, and its substrate, the hepatocyte growth factor (HGF), are implicated in the malignant progression of glioblastomas. In vivo detection of c-Met expression may be helpful in the diagnosis of malignant tumours. The C6 rat glioma model is a widely used intracranial brain tumour model used to study gliomas experimentally.We used a magnetic resonance imaging (MRI) molecular targeting agent to specifically tag the cell surface receptor, c-Met, with an anti-c-Met antibody (Ab) linked to biotinylated Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-albumin in rat gliomas to detect overexpression of this antigen in vivo. The anti-c-Met probe (anti-c-Met-Gd-DTPA-albumin) was administered intravenously, and as determined by an increase in MRI signal intensity and a corresponding decrease in regional T1 relaxation values, this probe was found to detect increased expression of c-Met protein levels in C6 gliomas. In addition, specificity for the binding of the anti-c-Met contrast agent was determined by using fluorescence microscopic imaging of the biotinylated portion of the targeting agent within neoplastic and 'normal' brain tissues following in vivo administration of the anti-c-Met probe. Controls with no Ab or with a normal rat IgG attached to the contrast agent component indicated no non-specific binding to glioma tissue. This is the first successful visualization of in vivo overexpression of c-Met in gliomas. [ABSTRACT FROM AUTHOR]