Development of a 0.014-in., anti-solenoid loop MR imaging guidewire for intravascular 3.0-T MR imaging

Purpose

This study aimed to develop a 0.014-in., anti-solenoid loop (ASL) magnetic resonance imaging guidewire (MRIG) for intravascular 3.0-T MR imaging.

Materials and Methods

We first designed the ASL MRIG, which was made of a coaxial cable with its extended inner conductor and outer conductor connected to two micro-anti-solenoids. We then evaluated in vitro the functionality of the ASL MRIG by imaging a “vessel” in a phantom and achieving signal-to-noise ratio (SNR) and SNR contour map of the new 0.014-in. ASL MRIG. Subsequently, we validated in vivo the feasibility of using the ASL MRIG to generate intravenous 3.0-T MR images of parallel iliofemoral arteries of near-human-sized living pigs.

Results

In vitro evaluation showed that the 0.014-in. ASL MRIG functioned well as a receiver coil with the 3.0-T MR scanner, clearly displaying the vessel wall with even distribution of MR signals and SNR contours from the ASL MRIG. Of the in vivo studies, the new ASL MRIG enabled us to successfully generate intravenous 3.0-T MR imaging of the iliofemoral arteries.

Conclusion

This study confirms that it is possible to build such small-looped MRIG at 0.014 in. for intravascular 3.0-T MR imaging.     

A method for the making and utility of gadolinium-labeled albumin microbubbles

Objective

Perfluorocarbon-exposed sonicated dextrose albumin microbubbles (PESDA) binds scavenger receptors and can be noninvasively imaged. To enhance imaging, gadolinium (Gd)-labeled PESDA was developed and tested in a model of vascular inflammation by magnetic resonance imaging (MRI).

Methods and Results

Purified human serum albumin (HSA) (5%) was labeled with Gd via the covalent binding of diethylenetriaminepentacetic acid. Abdominal aortic tissues in Sprague-Dawley rats (n=5 per group) were analyzed by 7-T MRI and scanning electron microscopy to evaluate PESDA binding. Labeling-purified 5% human albumin resulted in an average of 16.1 Gd atoms per albumin molecule as determined by atomic absorption. Forty-eight hours after balloon angioplasty, aortic tissue was enhanced with Gd-PESDA as compared to control tissue. 7-T MRI of explanted tissues was sensitive to the detection of retained PESDA. Enhancement of aortic tissue in vivo was present albeit to a lesser extent than explanted tissue from the same animals.

Conclusions

HSA was successfully labeled, and an albumin-based microbubble with Gd was synthesized. This contrast agent, Gd-PESDA, may serve as an additional agent for the MRI evaluation of innate inflammation and used to noninvasively image early vascular pathophysiologic processes.

Condensed Abstract

In this study, Gd-PESDA microbubbles and were synthesized and shown to detect the binding of these microbubbles using MRI in injured aortic tissue. The method for synthesizing Gd-PESDA is detailed, and the proposed utility of this new contrast agent is discussed.     

Application of multivariate analysis of TOF-SIMS spectra for studying the effect of high glucose intake on aortic lipid profile

Aim

To study the effect of long-term glucose feeding on aortic lipid composition by using the time of flight-secondary ion mass spectrometry (TOF-SIMS).

Method

Rats were divided into two groups, drinking water with or without 10% glucose from birth to 6 months of age. The aortic wall was dissected out, high-pressure frozen, freeze-fractured, freeze-dried and analyzed by TOF-SIMS using a Bismuth cluster ion source. Surface spectra were taken from standardized regions of the vessel wall.

Results

Different peaks, such as cholesterol, fatty acids (FAs) and diacylglycerols (DAGs), were identified by the principal component analysis as carries of variance between two groups. These peaks were then compared by conventional t-test. Our data showed that the intensity of cholesterol, but not FAs and DAGs, was significantly decreased in the glucose-drinking rat. Moreover, the long-term glucose intake changed ratios between different FAs in the aorta.

Conclusion

The long-term glucose intake led to decreased cholesterol intensity in the aortic wall and this effect was revealed through a global analytical approach with objective selection of significant variables.     

Quantitative assessment of mobile protein levels in human knee synovial fluid: feasibility of chemical exchange saturation transfer (proteinCEST) MRI of osteoarthritis

Purpose

To establish the feasibility of chemical exchange saturation transfer (proteinCEST) MRI in the differentiation of osteoarthritis (OA) knee joints from non-OA joints by detecting mobile protein and peptide levels in synovial fluid by determining their relative distribution.

Materials and Methods

A total of 25 knees in 11 men and 12 women with knee injuries were imaged using whole knee joint proteinCEST MRI sequence at 3 T. The joint synovial fluid was segmented and the asymmetric magnetization transfer ratio at 3.5 ppm MTR_asym (3.5 ppm) was calculated to assess protein content in the synovial fluid. The 85th percentile of synovial fluid MTR_asym (3.5 ppm) distribution profile was compared using the independent Student's t test. The diagnostic performance of the 85th percentile of synovial fluid MTR_asym (3.5 ppm) in differentiating OA and non-OA knee joints was evaluated.

Results

The 85th percentile of synovial fluid MTR_asym (3.5 ppm) in knee joints with OA was 8.6%±3.4% and significantly higher than that in the knee joints without OA (6.3%±1.4%, P<.05). A knee joint with an 85th percentile of synovial fluid MTR_asym (3.5 ppm) greater than 7.7% was considered to be an OA knee joint. With the threshold, the sensitivity, specificity and overall accuracy for differentiating knee joints with OA from the joints without OA were 54% (7/13), 92% (11/12) and 72% (18/25), respectively.

Conclusion

proteinCEST MRI appears feasible as a quantitative methodology to determine mobile protein levels in synovial fluid and identify patterns characteristic for OA disease.     

Paradoxical high signal intensity of hepatocellular carcinoma in the hepatobiliary phase of Gd-EOB-DTPA enhanced MRI: initial experience

Purpose

To describe the paradoxical high signal intensity of hepatocellular carcinoma (HCC) in the hepatobiliary phase on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI).

Materials and Methods

A database search was performed to identify cases of HCC that showed unusual prolonged enhancement in the hepatobiliary phase of Gd-EOB-DTPA MRI. All patients received 3.0-T liver MRI including precontrast T1-weighted images, T2-weighted images and a post Gd-EOB-DTPA-enhanced dynamic study. The signal intensity of HCC was measured at pre-enhanced, arterial, portal, delayed and hepatobiliary phase using regions of interest. Radiologic and pathologic correlation was performed for the paradoxically prolonged enhancing portion of HCC in the hepatobiliary phase.

Results

Four patients (all male, age range 44-70; mean 57.5 years) were included in this study. All patients showed HCC lesions that were low signal intensity (SI) on T1-WI, high SI on T2-WI, enhanced in arterial phase, and washed-out in delayed phase. All cases showed paradoxically high SI in hepatobiliary phase, which was unusual for HCC. Pathologically, they were all diagnosed as well-differentiated HCC with prominent cytoplasm and a bile secreting appearance.

Conclusion

HCC may demonstrate the prolonged high signal intensity at the hepatobiliary phase on Gd-EOB-DTPA enhanced MRI. These HCCs tended to be highly differentiated and to have prominent bile secretion.     

Micrometer-sized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering

Purpose

To examine mesenchymal stem cell (MSC) labeling with micrometer-sized iron oxide particles (MPIOs) for magnetic resonance imaging (MRI)-based tracking and its application to monitoring articular cartilage regeneration.

Methods

Rabbit MSCs were labeled using commercial MPIOs. In vitro MRI was performed with gradient echo (GRE) and spin echo (SE) sequences at 3T and quantitatively characterized using line profile and region of interest analysis. Ex vivo MRI of hydrogel-encapsulated labeled MSCs implanted within a bovine knee was performed with spoiled GRE (SPGR) and T_1ρ sequences. Fluorescence microscopy, labeling efficiency, and chondrogenesis of MPIO-labeled cells were also examined.

Results

MPIO labeling results in efficient contrast uptake and signal loss that can be visualized and quantitatively characterized via MRI. SPGR imaging of implanted cells results in ex vivo detection within native tissue, and T_1ρ imaging is unaffected by the presence of labeled cells immediately following implantation. MPIO labeling does not affect quantitative glycosaminoglycan production during chondrogenesis, but iron aggregation hinders extracellular matrix visualization. This aggregation may result from excess unincorporated particles following labeling and is an issue that necessitates further investigation.

Conclusion

This study demonstrates the promise of MPIO labeling for monitoring cartilage regeneration and highlights its potential in the development of cell-based tissue engineering strategies.     

Apparent diffusion coefficient of line scan diffusion image in normal prostate and prostate cancer—comparison with single-shot echo planner image

Purpose

This retrospective study was designed to evaluate the apparent diffusion coefficient (ADC) of line scan diffusion images (LSDI) in normal prostate and prostate cancer. Single-shot echo planner images (SS-EPI) were used for comparison.

Materials and Methods

Twenty prostate tumors were examined by conventional MRI in 14 patients prior to radical prostatectomy. All patients were examined with a 1.5-T MR imager (Signa CV/i ver. 9.1 GE Medical System Milwaukee, WI, USA). Diffusion-weighted MR imaging (DWI) using LSDI was performed with a pelvic phased-array coil, with b values of 5 and 800 s/mm². DWI using SS-EPI was performed with a body coil, with b values of 0 and 800 s/mm². The ADCs of each sequence for 14 normal prostate and 20 prostate cancers were histopathologically assessed. Signal-to-noise ratio (SNR) on DWI was estimated and compared for each sequence.

Results

The mean ADCs (±S.D.) of normal peripheral zones (PZ), transition zones (TZ) and cancer (in 10⁻³ mm²/s) that used LSDI were 1.42±0.12, 1.23±0.10 and 0.79±0.19, respectively. Those that used SS-EPI were 1.76±0.26, 1.38±0.20 and 1.05±0.27, respectively. Using unpaired t test (P<.05), we found a significant difference in each sequence between normal tissue (both PZ and TZ) and the cancer. Paired t test (P<.05) also registered a significant difference between LSDI and SS-EPI. Mean SNR for DWI using LSDI was 16.49±5.03, while the DWI using SS-EPI was 18.85±9.26. The difference between the SNR of each sequence was not statistically significant by paired t test.

Conclusion

We found that ADCs using LSDI and SS-EPI showed similar tendencies in the same patients. However, in all regions, LSDI ADCs had smaller standard deviations than SS-EPI ADCs.     

Detection of small intrahepatic metastases of hepatocellular carcinomas using diffusion-weighted imaging: comparison with conventional dynamic MRI

Purpose

The purpose of our study was to compare diffusion-weighted MR imaging (DWI) with conventional dynamic MRI in terms of the assessment of small intrahepatic metastases from hepatocellular carcinoma (HCC).

Materials and Methods

In 24 patients with multifocal, small (≤2 cm) intrahepatic metastatic foci of advanced HCC, a total of 134 lesions (≤1 cm, n=81; >1 cm, n=53) were subjected to a comparative analysis of hepatic MRI including static and gadopentetate dimeglumine-enhanced dynamic imaging, and DWI using a single-shot spin-echo echo-planar MRI (b values=50, 400 and 800 s/mm²), by two independent reviewers.

Results

A larger number of the lesions were detected and diagnosed as intrahepatic metastases on DWI [Reviewer 1, 121 (90%); Reviewer 2, 117 (87%)] than on dynamic imaging [Reviewer 1, 107 (80%); Reviewer 2, 105 (78%)] (P<.05). For the 81 smaller lesions (≤1 cm), DWI was able to detect more lesions than dynamic imaging [Reviewer 1, 68 (84%) vs. 56 (69%), P=.008; Reviewer 2, 65 (80%) vs. 55 (68%), P=.031], but there was no statistically significant difference between the two image sets for larger (>1 cm) lesions.

Conclusion

Due to its higher detection rate of subcentimeter lesions, DWI could be considered complementary to dynamic MRI in the diagnosis of intrahepatic metastases of HCCs.     

In vivo SNR in DENSE MRI; temporal and regional effects of field strength, receiver coil sensitivity and flip angle strategies

Aim

The influences on the signal-to-noise ratio (SNR) of Displacement ENcoding with Stimulated Echoes (DENSE) MRI of field strength, receiver coil sensitivity and choice of flip angle strategy have been previously investigated individually. In this study, all of these parameters have been investigated in the same setting, and a mutual comparison of their impact on SNR is presented.

Materials and methods

Ten healthy volunteers were imaged in a 1.5 T and a 3 T MRI system, using standard five- or six-channel cardiac coils as well as 32-channel coils, with four different excitation patterns. Variation of spatial coil sensitivity was assessed by regional SNR analysis.

Results

SNR ranging from 2.8 to 30.5 was found depending on the combination of excitation patterns, coil sensitivity and field strength. The SNR at 3 T was 53±26% higher than at 1.5 T (P<.001), whereas spatial differences of 59±26% were found in the ventricle (P<.001). Thirty-two-channel coils provided 52±29% higher SNR compared to standard five- or six-channel coils (P<.001). A fixed flip angle strategy provided an excess of 50% higher SNR in half of the imaged cardiac cycle compared to a sweeping flip angle strategy, and a single-phase acquisition provided a sixfold increase of SNR compared to a cine acquisition.

Conclusion

The effect of field strength and receiver coil sensitivity influences the SNR with the same order of magnitude, whereas flip angle strategy can have a larger effect on SNR. Thus, careful choice of imaging hardware in combination with adaptation of the acquisition protocol is crucial in order to realize sufficient SNR in DENSE MRI.     

Susceptibility weighted imaging in detecting hemorrhage in acute cervical spinal cord injury

Background and Purpose

Susceptibility weighted imaging (SWI) is sensitive to deoxyhemoglobin and blood products such as hemosiderin in detecting microbleeds in the brain. However, there are no studies on SWI in the spine cord injury so far. The purpose of this study was to evaluate the role of SWI in detecting hemorrhage in acute cervical spinal cord injury (SCI).

Materials and Methods

Twenty-three patients with a history of acute cervical spine trauma were studied. High-resolution SWI, gradient-echo (GRE) T2* weighted-image (T2*WI) and conventional magnetic resonance imaging (MRI) were performed on all patients within 15 days of the onset of injury. On the basis of the MRI findings, the patients were classified into four patterns: normal cord, spinal cord edema, spinal cord contusion and spinal cord hemorrhage. Quantitative analysis was performed by calculating and comparing the signal ratio of the hemorrhage to normal spinal cord on the same slice of T2*WI and SWI. All patients were clinically evaluated in follow-up. Twenty volunteers were also scanned as a control group.

Results

Out of 23 patients with a history of acute cervical spine trauma, 4 patients showed normal spinal cord on both conventional MRI and SWI, 8 had only spinal cord edema and 5 had contusion on conventional MRI, but SWI showed hemorrhage in 2 of the 5 patients with spinal contusion on conventional MRI; the other 6 patients had intraspinal hemorrhage on conventional MRI, and SWI proved hemorrhage in all these 6 patients. There was a significant difference between the signal ratios of hemorrhage to normal tissue on T2*WI and SWI (Z=2.34, P=.02).

Conclusion

Susceptibility weighted imaging is more sensitive than conventional MRI in detecting hemorrhage in acute cervical SCI. This technique could prove to be a useful tool in the routine evaluation of cervical SCI patients.     

Vibro-acoustography imaging of permanent prostate brachytherapy seeds in an excised human prostate - Preliminary results and technical feasibility

Objective:

The objective in this work is to investigate the feasibility of using a new imaging tool called vibro-acoustography (VA) as a means of permanent prostate brachytherapy (PPB) seed localization to facilitate post-implant dosimetry (PID).

Methods and materials:

Twelve OncoSeed (standard) and eleven EchoSeed (echogenic) dummy seeds were implanted in a human cadaver prostate. Seventeen seeds remained after radical retropubic prostatectomy. VA imaging was conducted on the prostate that was cast in a gel phantom and placed in a tank of degassed water. 2-D magnitude and phase VA image slices were obtained at different depths within the prostate showing location and orientation of the seeds.

Results:

VA demonstrates that twelve of seventeen (71%) seeds implanted were visible in the VA image, and the remainder were obscured by intra-prostatic calcifications. Moreover, it is shown here that VA is capable of imaging and locating PPB seeds within the prostate independent of seed orientation, and the resulting images are speckle free.

Conclusion:

The results presented in this research show that VA allows seed detection within a human prostate regardless of their orientation, as well as imaging intra-prostatic calcifications.     

Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling

Objective

To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis.

Methods

Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis.

Results

Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity.

Conclusion

Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.     

A robust graph-based segmentation method for breast tumors in ultrasound images

Objectives

This paper introduces a new graph-based method for segmenting breast tumors in US images.

Background and motivation

Segmentation for breast tumors in ultrasound (US) images is crucial for computer-aided diagnosis system, but it has always been a difficult task due to the defects inherent in the US images, such as speckles and low contrast.

Methods

The proposed segmentation algorithm constructed a graph using improved neighborhood models. In addition, taking advantages of local statistics, a new pair-wise region comparison predicate that was insensitive to noises was proposed to determine the mergence of any two of adjacent subregions.

Results and conclusion

Experimental results have shown that the proposed method could improve the segmentation accuracy by 1.5-5.6% in comparison with three often used segmentation methods, and should be capable of segmenting breast tumors in US images.     

Direct laser light enhancement of susceptibility of bacteria to gentamicin antibiotic

Objectives

To test the effect of pulsed (Q-switched) and continuous wave (CW) laser light at wavelength of 532 nm on the viability of free-living stationary phase bacteria with and without gentamicin (an antibiotic) treatment.

Methods

Free living stationary phase gram negative bacteria (Pseudomonas aeruginosa strain PAO1) was immersed in Luria Broth (LB) solution and exposed to Q-switched and CW lasers with and without the addition of the antibiotic gentamicin. Cell viability was determined at different time points.

Results

Laser treatment alone did not reduce cell viability compared to untreated control and the gentamicin treatment alone only resulted in a 0.5 log reduction in the viable count for P. aeruginosa. The combined laser and gentamicin treatment, however, resulted in a synergistic effect and viability was reduced by 8 logs for P. aeruginosa PAO1.

Conclusions

Combination of laser light with gentamicin shows an improved efficacy against P. aeruginosa.     

Hypocrellin B-mediated sonodynamic action induces apoptosis of hepatocellular carcinoma cells

Objective

The present study aims to investigate apoptosis of hepatocellular carcinoma cells induced by hypocrellin B-mediated sonodynamic action.

Methods

The hypocrellin B concentration was kept constant at 2.5 μM and cells from the hepatocellular carcinoma HepG2 cell line were exposed to ultrasound with an intensity of 0.46 W/cm² for 8 s. Cell cytotoxicity was quantified using an MTT assay 24 h after sonodynamic therapy (SDT) of hypocrellin B. Apoptosis was investigated using a flow cytometry with Annexin V-FITC and propidium iodine staining. Intracellular reactive oxygen species (ROS) levels were detected using a flow cytometry with 2,7-dichlorodihydrofluorecein diacetate (DCFH-DA) staining.

Results

The cytotoxicity of hypocrellin B-mediated sonodynamic action on HepG2 cells was significantly higher than those of other treatments including ultrasound alone, hypocrellin B alone and sham treatment. Flow cytometry showed that hypocrellin B-induced sonodynamic action markedly enhanced the apoptotic rate of HepG2 cells. Increased ROS was observed in HepG2 cells after being treated with hypocrellin B-mediated sonodynamic action.

Conclusions

Our data demonstrated that hypocrellin B-mediated sonodynamic action remarkably induced apoptosis of HepG2 cells, suggesting that apoptosis is an important mechanism of cell death induced by hypocrellin B-mediated SDT.     

Effects of therapeutic pulsed ultrasound and dimethylsulfoxide phonophoresis on oxidative stress parameters after injury induced by eccentric exercise

Introduction

The aim of the study was to evaluate the effects of TPU together with DMSO on oxidative stress parameters after eccentric exercise.

Methods

Thirty and six animals were divided in control; eccentric exercise (EE); EE + saline gel 0.9%; EE + TPU 0.8 W/cm²; EE + DMSO gel; EE + TPU + DMSO gel and submitted to one 90-min downhill run (1.0 km h⁻¹). TPU was used 2, 12, 24, 46 h after exercise session and 48 h after the animals were killed and the gastrocnemius muscles were surgically removed. Production of superoxide anion, creatine kinase (CK) levels, lipoperoxidation, carbonylation, and antioxidants enzymes were analyzed.

Results

Showed that TPU and gel-DMSO improved muscle healing. Moreover, superoxide anion production, TBARS level and protein carbonyls levels, superoxide dismutase and catalase activity were all decreased in the group TPU plus gel-DMSO.

Discussion

Our results show that DMSO is effective in the reduction of the muscular lesion and in the oxidative stress after eccentric exercise only when used with TPU.     

Evaluation of MRI issues for a new neurological implant,the Sensor Reservoir

Background and Purpose

A new neurological implant, the Sensor-Reservoir, was developed to provide a relative measurement of ICP, which permits a noninvasive technique to detect and localize occlusions in ventricular drainage systems and, thus, to identify mechanical damage to shunt valves. The “reservoir” of this device can be used to administer medication or a contrast agent, to extract cerebral spinal fluid (CSF), and with the possibility of directly measuring ICP. The Sensor-Reservoir was evaluated to identify possible MRI-related issues at 1.5-T/64-MHz and 3-T/128-MHz.

Materials and Methods

Standard testing techniques were utilized to evaluate magnetic field interactions (i.e., translational attraction and torque), MRI-related heating, and artifacts at 3-T for the Sensor-Reservoir. In addition, 12 samples of the Sensor-Reservoir underwent testing to determine if the function of these devices was affected by exposures to various MRI conditions at 1.5-T/64-MHz and 3-T/128-MHz.

Results

Magnetic field interactions for the Sensor-Reservoir were not substantial. The heating results indicated a highest temperature rise of 1.8 °C, which poses no patient risks. Artifacts were relatively small in relation to the size and shape of the Sensor-Reservoir, but may interfere diagnostically if the area of interest is near the device. All devices were unaffected by exposures to MRI conditions at 1.5-T/64-MHz and 3-T/128-MHz.

Conclusion

When specific guidelines are followed, the Sensor-Reservoir is “MR conditional” for patients undergoing MRI examinations at 3-T or less.     

Characterization of ultrasound-mediated destruction of drug-loaded microbubbles using an improved in vitro model

Introduction

Ultrasound mediated destruction of microbubbles (MBs) has become a promising tool for site specific drug and gene delivery. One of the most important properties of drug-loaded MBs is their destructibility by ultrasound. Therefore, the aim of this study was to establish a new in vitro model that allows evaluation of the kinetics of ultrasound-mediated MB destruction at near physiological conditions.In this work, a newly developed drug-loaded MB formulation was compared with unloaded MBs in order to assess the influence of drug-loading on their acoustic destructibility. Furthermore, drug-loaded MBs were compared to acoustically active lipospheres (AALs), comprising an additional layer of triacetin, as well as to a marketed MB contrast agent (SonoVue^®, Bracco Diagnostics, USA), used as standard.

Methods

MBs with phospholipid monolayer shells were produced by mechanical agitation of liposomal dispersions and octafluoropropane gas. AALs were accordingly produced by agitation of phospholipid-stabilized aqueous triacetin microemulsions with gas.The in vitro experimental setup for acoustic destructibility testing comprised a membrane cell, pressurized and brought to 37 °C in order to imitate human blood pressure and body temperature. The optimized egg-like cell shape provided optimal flow conditions and a minimized dead volume.Ultrasound with frequencies of 1 and 3 MHz and intensities, varying from 1 to 4 W/cm², was applied through a silicone membrane window to the cell. MB size distribution and concentration were measured by light blockage in equal time intervals during the sonication.

Results

The optimized in vitro setup demonstrated differences in the ultrasound destructibility of the MB formulations used. The fastest decay upon ultrasound exposure was found for SonoVue^®. Unloaded and drug-loaded MBs appeared to be comparably destructible to SonoVue^®. AALs were about 4.5-fold more stable than SonoVue^®. MB destructibility was also found to depend on particle diameter, corresponding to theoretical models described in the literature.

Conclusion

The optimized in vitro setup has rendered a fast and reliable laboratory tool for characterization of MB formulations.     

Evaluation of time-intensity curves in ductal carcinoma in situ (DCIS) and mastopathy obtained using dynamic contrast-enhanced magnetic resonance imaging

Purpose

The aim of this study was to retrospectively evaluate the ability of dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate between ductal carcinoma in situ (DCIS) and mastopathy by analyzing their signal intensities (SIs).

Methods

After the pre-contrast MRI was performed using a 1.5-T MRI system, DCE-MRI was performed four times following intravenous administration of contrast medium. We set the volumes of interest (VOIs) on the tumor and normal mammary gland and obtained the SIs in these VOIs. We calculated the entropy (EPY) in the pre-contrast (EPY0) and four post-contrast scans (EPY1, EPY2, EPY3, and EPY4 for the first, second, third and fourth scans, respectively) using the volume histogram method, and the wash-in (WR_in) and washout rates (WR_out) according to the Breast-Imaging Reporting and Data System developed by the American College of Radiology. We also calculated the early slope (Slope_early) from the pre- and post-contrast SIs in the tumor and normal gland. We evaluated the usefulness of the above parameters for differentiating between DCIS and mastopathy using the area under the receiver operating characteristic curve (Az).

Results

There were significant differences in EPY2 (P=.009), EPY3 (P=.017), EPY4 (P=.034), WR_in (P=.036), WR_out (P=.019), and Slope_early (P=.002) between DCIS and mastopathy. The average Az values were 0.67, 0.52, 0.64, 0.63, 0.67 and 0.70 for EPY2, EPY3, EPY4, WR_in, WR_out and Slope_early, respectively.

Conclusion

We evaluated the usefulness of various parameters calculated from SIs obtained by DCE-MRI for differentiating between DCIS and mastopathy. Our results suggested that Slope_early is more useful than EPYs, WR_in and WR_out.     

Blood oxygen level-dependent MRI for the monitoring of neoadjuvant chemotherapy in breast carcinoma: initial experience

Purpose

To determine the feasibility of using R2? map MRI for pretreatment diagnosis and monitoring of tumor response to neoadjuvant chemotherapy (NAC) in patients with breast cancer.

Material and Methods

Twenty-eight women with breast cancer, as evidenced by pathology, underwent MR imaging prior to and after chemotherapy. All patients were examined by conventional MRI and R2? map imaging. Subjects were divided into major histological response (MHR) and non-major histological response (NMHR) groups. Mean R2? values of cancerous and normal glandular tissues were measured before and following NAC. Differences in R2? and ΔR2?% values between these two groups were compared with paired or independent t tests. The relationship between ΔR2?% and histological response was examined using Spearman's correlation test.

Results

Before NAC, the average R2? values in carcinoma were lower than in normal glandular tissue (P<.05). After two to four cycles of NAC, the R2? values in carcinoma were increased (P<.05 ), but this change was not significant in normal glandular tissue. After NAC, ΔR2?% was significantly higher in MHR as compared to NMHR (P<.05). The ΔR2?% correlated with the histological response (r=0.581, P<.01).

Conclusion

In women undergoing NAC for breast cancer treatment, R2? and ΔR2?% appear to provide predictive information of tumor response which is probably associated with changes in tumor angiogenesis and tissue oxygenation. R2? map imaging of breasts may therefore be useful in monitoring tumor response to NAC.