Luning Wang

Magnetic Nanoparticle-Based Hyperthermia for Head & Neck Cancer in Mouse Models

In this study, magnetic iron oxide nanoparticle induced hyperthermia is applied for treatment of head and neck cancer using a mouse xenograft model of human head and neck cancer (Tu212 cell line). A hyperthermia system for heating iron oxide nanoparticles was developed by using alternating magnetic fields. Both theoretical simulation and experimental studies were performed to verify the thermotherapy effect. Experimental results showed that the temperature of the tumor center has dramatically elevated from around the room temperature to about 40oC within the first 5-10 minutes. Pathological studies demonstrate epithelial tumor cell destruction associated with the hyperthermia treatment.

Fe5C2 Nanoparticles with High MRI Contrast Enhancement for Tumor Imaging

An ancient material for magnetic resonance (MR) imaging: For the first time, Fe5C2 is prepared as colloidal stable nanoparticles with good aqueous stability. The nanoparticles boast strong magnetization, excellent chemical inertness, low toxicity, and one of the highest r2 relaxivities reported to date. These nanoparticles hold great potential in MR imaging as well as in other biomedical areas.

Surgical induction, histological evaluation, and MRI identification of cartilage necrosis in the distal femur in goats to model early lesions of osteochondrosis

OBJECTIVE Identify and interrupt the vascular supply to portions of the distal femoral articular-epiphyseal cartilage complex (AECC) in goat kids to induce cartilage necrosis, characteristic of early lesions of osteochondrosis (OC); then utilize magnetic resonance imaging (MRI) to identify necrotic areas of cartilage. DESIGN Distal femora were perfused and cleared in goat kids of various ages to visualize the vascular supply to the distal femoral AECC. Vessels located on the axial aspect of the medial femoral condyle (MFC) and on the abaxial side of the lateral trochlear ridge were transected in eight 4- to 5-day-old goats to induce cartilage necrosis. Goats were euthanized 1, 2, 3, 4, 5, 6, 9, and 10 weeks post operatively and operated stifles were harvested. Adiabatic T1ρ relaxation time maps of the harvested distal femora were generated using a 9.4 T MR scanner, after which samples were evaluated histologically. RESULTS Interruption of the vascular supply to the MFC caused lesions of cartilage necrosis in 6/8 goat kids that were demonstrated histologically. Adiabatic T1ρ relaxation time mapping identified these areas of cartilage necrosis in 5/6 cases. No significant findings were detected after transection of perichondrial vessels supplying the lateral trochlear ridge. CONCLUSIONS Cartilage necrosis, characteristic of early OC, can be induced by interrupting the vascular supply to the distal femoral AECC in goat kids. The ability of high field MRI to identify these areas of cartilage necrosis in the AECC using the adiabatic T1ρ sequence suggests that this technique may be useful in the future for the early diagnosis of OC.

T1 estimation for aqueous iron oxide nanoparticle suspensions using a variable flip angle SWIFT sequence

T1 quantification of contrast agents, such as super‐paramagnetic iron oxide nanoparticles, is a challenging but important task inherent to many in vivo applications in magnetic resonance imaging. In this work, a sweep imaging with Fourier transformation using variable flip angles (VFAs‐SWIFT) method was proposed to measure T1 of aqueous super‐paramagnetic iron oxide nanoparticle suspensions.

Improved Visualization of Cartilage Canals Using Quantitative Susceptibility Mapping

Purpose Cartilage canal vessels are critical to the normal function of epiphyseal (growth) cartilage and damage to these vessels is demonstrated or suspected in several important developmental orthopaedic diseases. High-resolution, three-dimensional (3-D) visualization of cartilage canals has recently been demonstrated using susceptibility weighted imaging (SWI). In the present study, a quantitative susceptibility mapping (QSM) approach is evaluated for 3-D visualization of the cartilage canals. It is hypothesized that QSM post-processing improves visualization of the cartilage canals by resolving artifacts present in the standard SWI post-processing while retaining sensitivity to the cartilage canals. Methods Ex vivo distal femoral specimens from 3- and 8-week-old piglets and a 1-month-old human cadaver were scanned at 9.4 T with a 3-D gradient recalled echo sequence suitable for SWI and QSM post-processing. The human specimen and the stifle joint of a live, 3-week-old piglet also were scanned at 7.0 T. Datasets were processed using the standard SWI method and truncated k-space division QSM approach. To compare the post-processing methods, minimum/maximum intensity projections and 3-D reconstructions of the processed datasets were generated and evaluated. Results Cartilage canals were successfully visualized using both SWI and QSM approaches. The artifactual splitting of the cartilage canals that occurs due to the dipolar phase, which was present in the SWI post-processed data, was eliminated by the QSM approach. Thus, orientation-independent visualization and better localization of the cartilage canals was achieved with the QSM approach. Combination of GRE with a mask based on QSM data further improved visualization. Conclusions Improved and artifact-free 3-D visualization of the cartilage canals was demonstrated by QSM processing of the data, especially by utilizing susceptibility data as an enhancing mask. Utilizing tissue-inherent contrast, this method allows noninvasive assessment of the vasculature in the epiphyseal cartilage in the developing skeleton and potentially increases the opportunity to diagnose disease of this tissue in the preclinical stages, when treatment likely will have increased efficacy.

Novel Application of Magnetic Resonance Imaging Demonstrates Characteristic Differences in Vasculature at Predilection Sites of Osteochondritis Dissecans

Background: Understanding the pathogenesis of osteochondrosis/osteochondritis dissecans and other developmental orthopaedic diseases that are thought to occur secondary to defects in vascular supply to growth/epiphyseal cartilage has been hampered by the inability to image the vasculature in this tissue. This is particularly true in human beings due to limitations of current imaging techniques and the lack of availability of appropriate cadaveric samples for histological studies. Hypothesis: Susceptibility-weighted imaging, an MRI sequence, allows identification of characteristic differences in the vascular architecture in species that are affected by osteochondrosis/osteochondritis dissecans on the femoral condyle (humans and pigs) versus a species that is free of the disease (goat). Study Design: Controlled laboratory study. Materials: Distal femora from cadavers of juvenile humans (n = 5), pigs (n = 3), and goats (n = 3) were scanned in a 9.4-T MRI scanner using susceptibility-weighted imaging. Three-dimensional reconstructions were created, and minimum intensity projections were calculated in 3 planes to enhance visualization of the vascular architecture. Results: Susceptibility-weighted imaging allowed clear visualization of the epiphyseal vasculature in all species. Vascular architecture, with vessels primarily arising from the perichondrium, was similar in humans and pigs, which are predisposed to osteochondrosis/osteochondritis dissecans, and was starkly different from that present in goats, a species in which there are no reports of osteochondrosis/osteochondritis dissecans. Furthermore, vessels in the distal femoral predilection site disappeared with age in humans in a pattern similar to that reported previously in pigs. Conclusion: Nearly identical vascular architecture at the shared primary predilection site of osteochondrosis/osteochondritis dissecans in the femoral condyles in human beings and pigs suggests that vascular failure, which is known to be central to the pathogenesis of this disease in pigs, may also play a role in humans. Clinical Relevance: This assumption of a shared pathogenesis is supported by the pattern of disappearance of vessels with age at the primary predilection site of osteochondritis dissecans in humans, which is essentially identical to that which has been reported in pigs. Susceptibility-weighted imaging will likely help further elucidate this potential relationship in the future.

Quantitative susceptibility mapping detects abnormalities in cartilage canals in a goat model of preclinical osteochondritis dissecans.

To use quantitative susceptibility mapping (QSM) to investigate changes in cartilage canals in the distal femur of juvenile goats after their surgical transection.

Improving detection specificity of iron oxide nanoparticles (IONPs) using the SWIFT sequence with long T2 suppression

In order to improve the detection specificity of iron oxide nanoparticles (IONPs) delivered to tumors, we embedded saturation pulses into the sweep imaging using Fourier transformation (SWIFT) sequence to suppress long T(2) tissues and fat. Simulation of the Bloch equation was first conducted to study behavior of the saturation pulses of various lengths under different T(2) and off-resonance conditions. MR experiments were then conducted using in vivo mouse xenografts and a phantom consisting of IONPs, vegetable oil, and explanted tumor specimen, without and with long T(2) suppression under a 7T magnetic field. For the in vivo study, arginine-glycine-aspartate (RGD) coated 10nm IONPs (RGD-IONPs) were delivered to tumors implanted in nude mice through both intra-tumor and intravenous injections. Histological studies confirmed that RGD-IONPs efficiently homed to tumors through RGD-integrin interaction. Compared to conventional SWIFT, the proposed method resulted in sufficient suppression on long T(2) species but less influence on short T(2) species. For both the in vivo and ex vivo studies, significantly improved contrast-to-noise ratio (CNR) was achieved between the IONPs and the long T(2) species.

Multiparametric MRI of Epiphyseal Cartilage Necrosis (Osteochondrosis) with Histological Validation in a Goat Model.

Purpose To evaluate multiple MRI parameters in a surgical model of osteochondrosis (OC) in goats. Methods Focal ischemic lesions of two different sizes were induced in the epiphyseal cartilage of the medial femoral condyles of goats at 4 days of age by surgical transection of cartilage canal blood vessels. Goats were euthanized and specimens harvested 3, 4, 5, 6, 9 and 10 weeks post-op. Ex vivo MRI scans were conducted at 9.4 Tesla for mapping the T1, T2, T1ρ, adiabatic T1ρ and TRAFF relaxation times of articular cartilage, unaffected epiphyseal cartilage, and epiphyseal cartilage within the area of the induced lesion. After MRI scans, safranin O staining was conducted to validate areas of ischemic necrosis induced in the medial femoral condyles of six goats, and to allow comparison of MRI findings with the semi-quantitative proteoglycan assessment in corresponding safranin O-stained histological sections. Results All relaxation time constants differentiated normal epiphyseal cartilage from lesions of ischemic cartilage necrosis, and the histological staining results confirmed the proteoglycan (PG) loss in the areas of ischemia. In the scanned specimens, all of the measured relaxation time constants were higher in the articular than in the normal epiphyseal cartilage, consistently allowing differentiation between these two tissues. Conclusions Multiparametric MRI provided a sensitive approach to discriminate between necrotic and viable epiphyseal cartilage and between articular and epiphyseal cartilage, which may be useful for diagnosing and monitoring OC lesions and, potentially, for assessing effectiveness of treatment interventions.

In vivo quantification of SPIO nanoparticles for cell labeling based on MR phase gradient images

Along with the development of modern imaging technologies, contrast agents play increasingly important roles in both clinical applications and scientific research. Super-paramagnetic iron oxide (SPIO) nanoparticles, a negative contrast agent, have been extensively used in magnetic resonance imaging (MRI), such as in vivo labeling and tracking of cells. However, there still remain many challenges, such as in vivo quantification of SPIO nanoparticles. In this work, an MR phase gradient-based method was proposed to quantify the SPIO nanoparticles. As a calibration, a phantom experiment using known concentrations (10, 25, 50, 100, 150 and 250 µg/ml) of SPIO was first conducted to verify the proposed quantification method. In a following in vivo experiment, C6 glioma cells labeled with SPIO nanoparticles were implanted into flanks of four mice, which were scanned 1-3 days post-injection for in vivo quantification of SPIO concentration. The results showed that the concentration of SPIO nanoparticles could be determined in both phantom and in vivo experiments using the developed MR phase gradients approach.