Use of multiparametric MRI to characterize uterine fibroid tissue types

Background: Although the biological characteristics of uterine fibroids (UF) have implications for therapy choice and effectiveness, there is limited MRI data about these characteristics. Currently, the Funaki classification and Scale

Quantitative analysis of the microstructural homogeneity of zirconia-toughened alumina composites

The Voronoi diagram approach was applied to quantify the level of microstructural homogeneity of ceramic ZTA samples. From SEM pictures of polished cross-sections of ZTA samples a point pattern representing the distribution of the zirconia phase in the composite was generated. This point pattern was converted into a Voronoi diagram. The level of microstructural homogeneity was quantified by statistical analysis of the relevant properties (area, perimeter and number of faces) of the Voronoi polygons. A dimensionless parameter defining the level of microstructural homogeneity was calculated from the different sets of statistical data. The calculated parameters indicated significant differences in homogeneity between the ZTA samples. These differences were in qualitative agreement with previously published wear rates of the same ZTA composites. This illustrates the relevance of microstructural homogeneity for wear performance

Interleaved Mapping of Temperature and Longitudinal Relaxation Rate to Monitor Drug Delivery During Magnetic Resonance-Guided High-Intensity Focused Ultrasound-Induced Hyperthermia

Objectives: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a method to heat lesions noninvasively to a stable, elevated temperature and a well-suited method to induce local hyperthermia (41 degrees C-43 degrees C) in deep-seated tissues. Magnetic Resonance (MR) imaging provides therapy planning on anatomical images and offers temperature feedback based on near-realtime MR thermometry. Although constant acquisition of MR thermometry data is crucial to ensure prolonged hyperthermia, it limits the freedom to perform measurements of other MR parameters, which are of interest during hyperthermia treatments. In image-guided drug delivery applications, co-encapsulation of paramagnetic MR contrast agents with a drug inside temperature-sensitive liposomes (TSLs) allows to visualize hyperthermia-triggered drug delivery through changes of the longitudinal relaxation rate R-1. While the drug accumulates in the heated tumor tissue, R1 changes can be used for an estimate of the tumor drug concentration. The main objective of this study was to demonstrate that interleaved MR sequences are able to monitor temperature with an adequate temporal resolution and could give a reasonable estimate of the achieved tumor drug concentration through R-1 changes. To this aim, in vitro validation tests and an in vivo proof-of- concept study were performed. Materials and Methods: All experiments were performed on a clinical 3-T MR-HIFU system adapted with a preclinical setup. The validity of the R-1 values and the temperature maps stability were evaluated in phantom experiments and in ex vivo porcine muscle tissue. In vivo experiments were performed on rats bearing a 9L glioma tumor on their hind limb. All animals (n = 4 HIFU-treated, n = 4 no HIFU) were injected intravenously with TSLs co-encapsulating doxorubicin and gadoteridol as contrast agent. The TSL injection was followed by either 2 times 15 minutes of MR-HIFU-induced hyperthermia or a sham treatment. R-1 maps were acquired before, during, and after sonication, using a single slice Inversion Recovery Look-Locker (IR-LL) sequence (field of view [FOV], 50 x 69 mm(2); in-plane resolution, 0.52 x 0.71 mm2; slice thickness, 3 mm; 23 phases of 130 milliseconds; 1 full R1 map every 2 minutes). The R1 maps acquired during treatment were interleaved with 2 perpendicular proton resonance frequency shift (PRFS) MR thermometry slices (dynamic repetition time, 8.6 seconds; FOV, 250 x 250 mm(2); 1.4 x 1.4 mm(2) in-plane resolution; 4 mm slice thickness). Tumor doxorubicin concentrations were determined fluorometrically. Results: In vitro results showed a slight but consistent overestimation of the measured R1 values compared with calibrated R-1 values, regardless whether the R1 was acquired with noninterleaved IR-LL or interleaved. The average treatment cell temperature had a slightly higher temporal standard deviation for the interleaved PRFS sequence compared with the noninterleaved PRFS sequence (0.186 degrees C vs 0.101 degrees C, respectively). The prolonged time in between temperature maps due to the interleaved IR-LL sequence did not degrade the temperature stability during MR-HIFU treatment (T-average = 40.9 degrees C +/- 0.3 degrees C). Upon heat treatment, some tumors showed an R-1 increase in a large part of the tumor while other tumors hardly showed any Delta R-1. The tumor doxorubicin concentration showed a linear correlation with the average Delta R-1 during both sonications (n = 8, R-adj(2) = 0.933), which was higher than for the Delta R1 measured after tumor cooldown (averaged for both sonications, n = 8, R-adj(2) = 0.877). Conclusions: The new approach of interleaving different MR sequences was applied to simultaneously acquire R-1 maps and PRFS thermometry scans during a feedback-controlled MR-HIFU-induced hyperthermia treatment. Interleaved acquisition did not compromise speed or accuracy of each scan. The Delta R-1 acquired during treatment was used to visualize and quantify hyperthermia-triggered release of gadoteridol from TSLs and better reflected the intratumoral doxorubicin concentrations than the Delta R-1 measured after cooldown of the tumor, exemplifying the benefit of interleaving R-1 maps with temperature maps during drug delivery. Our study serves as an example for interleaved MR acquisition schemes, which introduce a higher flexibility in speed, sequence optimization, and timing

Thermal combination therapies for local drug delivery by magnetic resonance-guided high-intensity focused ultrasound

Several thermal-therapy strategies such as thermal ablation, hyperthermia-triggered drug delivery from temperature-sensitive liposomes (TSLs), and combinations of the above were investigated in a rhabdomyosarcoma rat tumor model (n = 113). Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) was used as a noninvasive heating device with precise temperature control for image-guided drug delivery. For the latter, TSLs were prepared, coencapsulating doxorubicin (dox) and [Gd(HPDO3A)(H2O)], and injected in tumor-bearing rats before MR-HIFU treatment. Four treatment groups were defined: hyperthermia, ablation, hyperthermia followed by ablation, or no HIFU. The intratumoral TSL and dox distribution were analyzed by single-photon emission computed tomography (SPECT)/computed tomography (CT), autoradiography, and fluorescence microscopy. Dox biodistribution was quantified and compared with that of nonliposomal dox. Finally, the treatment efficacy of all heating strategies plus additional control groups (saline, free dox, and Caelyx) was assessed by tumor growth measurements. All HIFU heating strategies combined with TSLs resulted in cellular uptake of dox deep into the interstitial space and a significant increase of tumor drug concentrations compared with a treatment with free dox. Ablation after TSL injection showed [Gd(HPDO3A)(H2O)] and dox release along the tumor rim, mirroring the TSL distribution pattern. Hyperthermia either as standalone treatment or before ablation ensured homogeneous TSL, [Gd(HPDO3A)(H2O)], and dox delivery across the tumor. The combination of hyperthermia-triggered drug delivery followed by ablation showed the best therapeutic outcome compared with all other treatment groups due to direct induction of thermal necrosis in the tumor core and efficient drug delivery to the tumor rim

Quantification of left ventricular volumes and ejection fraction in mice using PET, compared with MRI

PET has become an important noninvasive imaging technique in cardiovascular research for the characterization of mouse models in vivo. This modality offers unique insight into biochemical changes on a molecular level, with excellent sensitivity. However, morphologic and functional changes may be of equal importance for a thorough assessment of left ventricular (LV) pathophysiology. Although echocardiography and MRI are widely considered the imaging techniques of choice for the assessment of these parameters, their use with PET considerably increases study complexity and decreases cost- and time-efficiency. In this study, a novel method for the additional quantification of LV volumes and ejection fraction (EF) from PET was evaluated using cardiac MRI as the reference method. The radiolabeled glucose derivative 18F-FDG was injected into 33 mice (6 mice with previous permanent occlusion of the left anterior descending artery [LAD], 15 mice with a temporary 30-min occlusion of the LAD, and 12 mice without previous surgery). 18F-FDG uptake within the LV myocardium was measured using a dedicated small-animal PET scanner. After we reconstructed the images into 16 electrocardiogram (ECG)-gated frames, we determined the LV cavity volumes in end-diastole (EDV) and end-systole (ESV) and the EF using a semiautomatic segmentation algorithm based on elastic surfaces. A 6.3-T cardiac MRI examination was performed in the same animals using an ECG-triggered and respiratory-gated multislice cine sequence. The MR images were segmented with a semiautomatic algorithm using commercially available software. Overall, measurements from PET agreed well with those obtained by MRI. Mean EDV and ESV were slightly overestimated by PET (86+/-43 microL and 44+/-42 microL), compared with MRI (73+/-44 microL and 41+/-46 microL); mean (+/-SD) EF was similar (PET, 55+/-19 microL; MRI, 54+/-18 microL). Correlation between PET and MRI was excellent for EDV (0.97) and ESV (0.96) and good for EF (0.86). The slope of the regression line was nearly perfect for EDV (0.98) and EF (1.01) and slightly below 1 for ESV (0.90), indicating a good separation of abnormal and normal values with PET. The y-intercept was above zero for EDV (15 microL) and ESV (7 microL) and near to zero for EF (0.2%). The quantification of LV volumes and EF in mice with PET is both efficient and accurate. This method allows for combined molecular and functional imaging of the left ventricle within a single scan, obviating additional sophisticated MRI in many case

Magnetic Resonance Imaging of regional cardiac function in the mouse

In this paper we introduce an improved harmonic phase (HARP) analysis for complementary spatial modulation of magnetization (CSPAMM) tagging of the mouse left ventricular wall, which enables the determination of regional displacement fields with the same resolution as the corresponding CINE anatomical images. CINE MRI was used to measure global function, such as the ejection fraction. The method was tested on two healthy mouse hearts and two mouse hearts with a myocardial infarction, which was induced by a ligation of the left anterior descending coronary artery. We show that the regional displacement fields can be determined. The mean circumferential strain for the left ventricular wall of one of the healthy mice was –0.09 ± 0.04 (mean ± standard deviation), while for one of the infarcted mouse hearts strains of –0.02 ± 0.02 and –0.10 ± 0.03 were found in the infarcted and remote regions, respectively

Interleaved mapping of temperature and longitudinal relaxation rate to monitor drug delivery during magnetic resonance-guided high-intensity focused ultrasound-induced hyperthermia

\u3cp\u3eObjectives Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a method to heat lesions noninvasively to a stable, elevated temperature and a well-suited method to induce local hyperthermia (41°C-43°C) in deep-seated tissues. Magnetic Resonance (MR) imaging provides therapy planning on anatomical images and offers temperature feedback based on near-real-time MR thermometry. Although constant acquisition of MR thermometry data is crucial to ensure prolonged hyperthermia, it limits the freedom to perform measurements of other MR parameters, which are of interest during hyperthermia treatments. In image-guided drug delivery applications, co-encapsulation of paramagnetic MR contrast agents with a drug inside temperature-sensitive liposomes (TSLs) allows to visualize hyperthermia-triggered drug delivery through changes of the longitudinal relaxation rate R1. While the drug accumulates in the heated tumor tissue, R1 changes can be used for an estimate of the tumor drug concentration. The main objective of this study was to demonstrate that interleaved MR sequences are able to monitor temperature with an adequate temporal resolution and could give a reasonable estimate of the achieved tumor drug concentration through R1 changes. To this aim, in vitro validation tests and an in vivo proof-of-concept study were performed. Materials and Methods All experiments were performed on a clinical 3-T MR-HIFU system adapted with a preclinical setup. The validity of the R1 values and the temperature maps stability were evaluated in phantom experiments and in ex vivo porcine muscle tissue. In vivo experiments were performed on rats bearing a 9L glioma tumor on their hind limb. All animals (n = 4 HIFU-treated, n = 4 no HIFU) were injected intravenously with TSLs co-encapsulating doxorubicin and gadoteridol as contrast agent. The TSL injection was followed by either 2 times 15 minutes of MR-HIFU-induced hyperthermia or a sham treatment. R1 maps were acquired before, during, and after sonication, using a single slice Inversion Recovery Look-Locker (IR-LL) sequence (field of view [FOV], 50 × 69 mm2; in-plane resolution, 0.52 × 0.71 mm2; slice thickness, 3 mm; 23 phases of 130 milliseconds; 1 full R1 map every 2 minutes). The R1 maps acquired during treatment were interleaved with 2 perpendicular proton resonance frequency shift (PRFS) MR thermometry slices (dynamic repetition time, 8.6 seconds; FOV, 250 × 250 mm2; 1.4 × 1.4 mm2 in-plane resolution; 4 mm slice thickness). Tumor doxorubicin concentrations were determined fluorometrically. Results In vitro results showed a slight but consistent overestimation of the measured R1 values compared with calibrated R1 values, regardless whether the R1 was acquired with noninterleaved IR-LL or interleaved. The average treatment cell temperature had a slightly higher temporal standard deviation for the interleaved PRFS sequence compared with the noninterleaved PRFS sequence (0.186°C vs 0.101°C, respectively). The prolonged time in between temperature maps due to the interleaved IR-LL sequence did not degrade the temperature stability during MR-HIFU treatment (Taverage = 40.9°C ± 0.3°C). Upon heat treatment, some tumors showed an R1 increase in a large part of the tumor while other tumors hardly showed any ΔR1. The tumor doxorubicin concentration showed a linear correlation with the average ΔR1 during both sonications (n = 8, R2adj = 0.933), which was higher than for the ΔR1 measured after tumor cooldown (averaged for both sonications, n = 8, R2adj = 0.877). Conclusions The new approach of interleaving different MR sequences was applied to simultaneously acquire R1 maps and PRFS thermometry scans during a feedback-controlled MR-HIFU-induced hyperthermia treatment. Interleaved acquisition did not compromise speed or accuracy of each scan. The ΔR1 acquired during treatment was used to visualize and quantify hyperthermia-triggered release of gadoteridol from TSLs and better reflected the intratumoral doxorubicin concentrations than the ΔR1 measured after cooldown of the tumor, exemplifying the benefit of interleaving R1 maps with temperature maps during drug delivery. Our study serves as an example for interleaved MR acquisition schemes, which introduce a higher flexibility in speed, sequence optimization, and timing.\u3c/p\u3