Magnetic Resonance Imaging Monitoring Research Articles

Magnetic Resonance Imaging for Monitoring of Magnetic Polyelectrolyte Capsule In Vivo Delivery

Layer-by-layer (LbL) assembled polyelectrolyte capsules have been widely studied as promising delivery systems due to their well-controlled architectures. Although their potential applications in vitro have been widely investigated, at present, it is still a challenging task to track their real-time delivery in vivo, where and how they would be located following their administration. In this work, the noninvasive magnetic resonance imaging (MRI) technique was applied to monitor the delivery of polyelectrolyte capsules in vivo, incorporating magnetite nanoparticles as imaging components. First, MRI scan was performed over 6 h after sample administration at the magnetic field of 3.0 T; magnetic capsules, both poly(allylamine hydrochloride)/poly(styrenesulfonate sodium salt)-based and poly-l-arginine hydrochloride/dextran sulfate (Parg/DS)-based, were detected mostly in the liver region, where the transverse relaxation time (T2) was shortened and hypointense images were visualized, demonstrating a contrast-enhanced MRI effect between liver and adjacent tissue. A continuous MRI scan found that the contrast-enhanced MRI effect can last up to 30 h; in the mean time, the Parg/DS-based capsules with smaller diameter were found to have a pronounced clearance effect, which resulted in a weakened MRI effect in the liver. No obvious toxicity was found in animal studies, and all mice survived after MRI scans. Histology study provided evidences to support the MRI results, and also revealed the destination of these magnetic capsules over 30 h after administration.

MRI-Monitored Intra-Shunt Local Agent Delivery of Motexafin Gadolinium: Towards Improving Long-Term Patency of TIPS

BackgroundTransjugular intrahepatic portosystemic shunt (TIPS) has become an important and effective interventional procedure in treatment of the complications related to portal hypertension. Although the primary patency of TIPS has been greatly improved due to the clinical application of cover stent-grafts, the long-term patency is still suboptimal. This study was to investigate the feasibility of using magnetic resonance imaging (MRI)-monitored intra-shunt local agent delivery of motexafin gadolinium (MGd) into shunt-vein walls of TIPS. This new technique aimed to ultimately inhibit shuntstenosis of TIPS.MethodologyHuman umbilical vein smooth muscle cells (SMCs) were incubated with various concentrations of MGd, and then examed by confocal microscopy and T1-map MRI. In addition, the proliferation of MGd-treated cells was evaluated. For in vivo validation, seventeen pigs underwent TIPS. Before placement of the stent, an MGd/trypan-blue mixture was locally delivered, via a microporous balloon, into eleven shunt-hepatic vein walls under dynamic MRI monitoring, while trypan-blue only was locally delivered into six shunt-hepatic vein walls as serve as controls. T1-weighted MRI of the shunt-vein walls was achieved before- and at different time points after agent injections. Contrast-to-noise ratio (CNR) of the shunt-vein wall at each time-point was measured. Shunts were harvested for subsequent histology confirmation.Principal FindingsIn vitro studies confirmed the capability of SMCs in uptaking MGds in a concentration-dependent fashion, and demonstrated the suppression of cell proliferation by MGds as well. Dynamic MRI displayed MGd/blue penetration into the shunt-vein walls, showing significantly higher CNR of shunt-vein walls on post-delivery images than on pre-delivery images (49.5±9.4 vs 11.2±1.6, P<0.01), which was confirmed by histology.ConclusionResults of this study indicate that MRI-monitored intra-shunt local MGd delivery is feasible and MGd functions as a potential therapeutic agent to inhibit the proliferation of SMCs, which may open alternative avenues to improve the long-term patency of TIPS.

High Temporal Resolution Parametric MRI Monitoring of the Initial Ischemia/Reperfusion Phase in Experimental Acute Kidney Injury

Ischemia/reperfusion (I/R) injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI). There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI) may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T2* and T2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

Noninvasive and targeted gene delivery into the brain using microbubble-facilitated focused ultrasound.

Recombinant adeno-associated viral (rAAV) vectors are potentially powerful tools for gene therapy of CNS diseases, but their penetration into brain parenchyma is severely limited by the blood-brain barrier (BBB) and current delivery relies on invasive stereotactic injection. Here we evaluate the local, targeted delivery of rAAV vectors into the brains of mice by noninvasive, reversible, microbubble-facilitated focused ultrasound (FUS), resulting in BBB opening that can be monitored and controlled by magnetic resonance imaging (MRI). Using this method, we found that IV-administered AAV2-GFP (green fluorescence protein) with a low viral vector titer (1×109 vg/g) can successfully penetrate the BBB-opened brain regions to express GFP. We show that MRI monitoring of BBB-opening could serve as an indicator of the scale and distribution of AAV transduction. Transduction peaked at 3 weeks and neurons and astrocytes were affected. This novel, noninvasive delivery approach could significantly broaden the application of AAV-viral-vector-based genes for treatment of CNS diseases.

Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery.

This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability.

P2.13 Image-Guided and Targeted Therapy Using Theranostic Nanoparticles for Personalized Cancer Treatment

ABSTRACT Highly heterogeneous cancer cells represent the major challenge in clinical oncology for the treatment of human cancers. Novel therapeutic approaches that enable the application of personalized therapy for cancer patients hold great promise for effective treatment while minimizing systemic toxicity. We have developed an integrated cancer image-therapy protocol that takes advantages of multifunctionality of theranostic nanoparticles and advanced molecular imaging methods for biomarker-targeted tumor imaging and drug delivery, MRI monitoring therapeutic response, and optical image-guided surgery. Multifunctional magnetic iron oxide nanoparticles (IONPs) developed by our group are targeted to epidermal growth factor receptor, Her-2/Neu, and urokinase plasminogen activator receptor, which are biomarkers highly expressed in many types of human cancers. These receptor-targeted IONPs have capacity to carry single or multiple therapeutic agents for drug delivery, near infrared fluorescence and spectroscopic optical imaging, and magnetic resonance imaging (MRI). They are also designed to overcome physical and intrinsic barriers that reduce efficiency of drug delivery and confer drug resistance in human cancers. We have shown specificity and sensitivity of optical and MR imaging using the nanoparticles as targeted molecular contrast agents in orthotopic human breast, pancreatic, and ovarian cancer xenograft models. The development of biomarker targeted MRI nanoparticle probes should allow determining the level of biomarker expression in tumors using a non-invasive imaging approach for selection of the appropriate patients for targeted therapy. Based on the targeted imaging nanoparticles, we further developed methods to encapsulate or conjugate chemotherapy drugs into the nanoparticles. Efficacy of targeted therapy and MRI-monitoring drug delivery and response after systemic delivery of the theranostic nanoparticles has been demonstrated in orthotopic human breast, pancreatic and ovarian cancer xenograft models in nude mice. Since drug resistant residual tumors contain nanoparticles that produce optical signals, we applied hand-held optical imaging devices for detection and removal of drug resistant tumor lesions in the surgical cavity to prevent local recurrence and distant metastasis. The ultimate goal of our research is to translate this biomarker targeted therapy and image-guided treatment and surgery protocol into clinical applications for personalized management of cancer patients. Download : Download full-size image Fig. 1 . An integrated therapy-imaging approach for personalized therapy and effective treatment of drug-resistant cancers

Prevalence of Nonstenosing, Complicated Atherosclerotic Plaques in Cryptogenic Stroke

Our goal was to assess the prevalence of complicated American Heart Association (AHA) lesion type VI plaques in the carotid arteries of patients with cryptogenic stroke. In up to 40% of ischemic stroke patients, no definite cause can be established despite extensive workup (i.e., cryptogenic stroke). To test the hypothesis if nonstenosing complicated carotid plaques may be the underlying etiology in some of these patients, we used high-resolution black-blood carotid magnetic resonance imaging (MRI), which can quantitatively assess plaque composition and morphology with good correlation to histopathology. Specifically, we focused on AHA type VI plaques, which are characterized by hemorrhage, thrombus, or fibrous cap rupture. Thirty-two consecutive patients (22 male; mean age 71.7 ± 11.9 years) with cryptogenic stroke and nonstenosing (<50%) eccentric carotid plaques were recruited from a single stroke unit. All patients underwent extensive clinical workup (brain MRI, duplex sonography, electrocardiography and Holter monitoring, transthoracic and transesophageal echocardiography, and laboratory investigations) to exclude other causes of stroke. All patients received a black-blood carotid MRI at 3-T with fat-saturated pre- and post-contrast T-1-, proton density-, and T-2-weighted and time-of-flight images using surface coils and parallel imaging techniques. Prevalence of AHA type VI plaque was determined in both carotid arteries on the basis of previously published MRI criteria. AHA type VI plaques were found in 12 of 32 arteries (37.5%) ipsilateral to the stroke, whereas there were no AHA type VI plaques contralateral to the stroke (p = 0.001). The most common diagnostic feature of AHA type VI plaques was intraplaque hemorrhage (75%), followed by fibrous plaque rupture (50%) and luminal thrombus (33%). This pilot study suggests that arterio-arterial embolism from complicated, nonstenosing carotid atherosclerotic plaques may play a role in a subgroup of patients previously diagnosed with cryptogenic stroke. To further evaluate the significance of AHA type VI plaques in cryptogenic stroke, future studies will have to analyze both clinical and imaging follow-up data, including event rates for secondary strokes.

Diagnosis of Iron Overload and Heart Disease by Magnetic Resonance Imaging

The use of Magnetic resonance imaging (MRI) to estimate tissue iron was initiated nearly three decades ago but has only become a practical reality in the last ten years. MRI is most often used to estimate hepatic and cardiac iron in patients with thalassemia or sickle cell disease and has largely replaced liver biopsy for liver iron quantification. The ability of MRI to image extra hepatic organs has really transformed our understanding of iron mediated toxicity in transfusional siderosis. For decades, iron cardiomyopathy was the leading cause of death in thalassemia major, but it is now relatively rare in centers with regular MRI screening. Early recognition of cardiac iron loading allows more gentle modifications of iron chelation therapy prior to life threatening organ dysfunction. Serial MRI evaluations have demonstrated differential kinetics of uptake and clearance among the difference organs of the body. Although elevated serum ferritin and liver iron concentration increase the risk of cardiac and endocrine toxicities, extra hepatic iron deposition and toxicity occurs in many patients despite having low total body iron stores; there is no safe liver iron level in chronically transfused patients. Instead, the type, dose, and pattern of iron chelation therapy all contribute to whether cardiac iron accumulation will occur. These observations, coupled with the advent of increasing options for iron chelation therapy, are allowing clinicians to more appropriately tailor chelation therapy to individual patient needs, producing greater efficacy with fewer toxicities. With the decline in cardiac mortality, future frontiers in MRI monitoring including better prevention of endocrine toxicities, particularly hypogonadotropic hypogonadism and diabetes. These organs also serve as early warning signals for inadequate control of non-transferrin bound iron, a risk factor for cardiac iron loading. Thus MRI assessment of extra hepatic iron stores is a critical monitoring tool for chronically transfused patients. Further prospective work is necessary to determine whether markers of endocrine and exocrine pancreatic function can be used as surrogates of cardiac risk in regions where MRI is not available.

Detection of pancreatic islet allograft impairment in advance of functional failure using magnetic resonance imaging

This study evaluated the ability of magnetic resonance imaging (MRI) to predict failure of pancreatic islets (PI) transplanted into the hepatic portal vein. Brown-Norway (n = 18) and Lewis (n = 6) rats received islets isolated from Lewis donors. The rejection process in Brown-Norway recipients was mitigated by two different immunosuppressive regimens [tacrolimus + hydrocortisone for 3 months (n = 6) or tacrolimus for 12 days (n = 12)]. Longitudinal MRI monitoring of recipients at post-transplantation weeks 1, 2, 3, 4, 6, 8, 10, and 12 confirmed the ability to detect SPIO labeled PI after transplantation into the liver. The relative number of MRI signals related to PI isografts remained stable up to study completion. Recipients of PI allografts were normoglycemic until the end of study; signals declined gradually to 44 ± 17% in these animals. In animals with islets failure during post-transplant week 12, the number of signals decreased to 25 ± 10% of initial values. The difference between groups (islet function/failed) became significant post-transplant week 3. Our data demonstrate that the MRI changes attributable to rejection become apparent within 3 weeks after transplantation, i.e. at least 8 weeks before functional allograft failure.

Impact of Iron Assessment by MRI

The use of magnetic resonance imaging (MRI) to estimate tissue iron was conceived in the 1980s, but has only become a practical reality in the last decade. The technique is most often used to estimate hepatic and cardiac iron in patients with transfusional siderosis and has largely replaced liver biopsy for liver iron quantification. However, the ability of MRI to quantify extrahepatic iron has had a greater impact on patient care and on our understanding of iron overload pathophysiology. Iron cardiomyopathy used to be the leading cause of death in thalassemia major, but is now relatively rare in centers with regular MRI screening of cardiac iron, through earlier recognition of cardiac iron loading. Longitudinal MRI studies have demonstrated differential kinetics of uptake and clearance among the difference organs of the body. Although elevated serum ferritin and liver iron concentration (LIC) increase the risk of cardiac and endocrine toxicities, some patients unequivocally develop extrahepatic iron deposition and toxicity despite having low total body iron stores. These observations, coupled with the advent of increasing options for iron chelation therapy, are allowing clinicians to more appropriately tailor chelation therapy to individual patient needs, producing greater efficacy with fewer toxicities. Future frontiers in MRI monitoring include improved prevention of endocrine toxicities, particularly hypogonadotropic hypogonadism and diabetes.

Development and Evaluation of an Actuated MRI-Compatible Robotic System for MRI-Guided Prostate Intervention

This paper reports the design, development, and magnetic resonance imaging (MRI) compatibility evaluation of an actuated transrectal prostate robot for MRI-guided needle intervention in the prostate. The robot performs actuated needle MRI-guidance with the goals of providing (i) MRI compatibility, (ii) MRI-guided needle placement with accuracy sufficient for targeting clinically significant prostate cancer foci, (iii) reducing interventional procedure times (thus increasing patient comfort and reducing opportunity for needle targeting error due to patient motion), (iv) enabling real-time MRI monitoring of interventional procedures, and (v) reducing the opportunities for error that arise in manually actuated needle placement. The design of the robot, employing piezo-ceramic-motor actuated needle guide positioning and manual needle insertion, is reported. Results of a MRI compatibility study show no reduction of MRI signal-to-noise-ratio (SNR) with the motors disabled. Enabling the motors reduces the SNR by 80% without RF shielding, but SNR is only reduced by 40% to 60% with RF shielding. The addition of radio-frequency shielding is shown to significantly reduce image SNR degradation caused by the presence of the robotic device. An accuracy study of MRI-guided biopsy needle placements in a prostate phantom is reported. The study shows an average in-plane targeting error of 2.4 mm with a maximum error of 3.7 mm. These data indicate the system's needle targeting accuracy is similar to that obtained with a previously reported manually actuated system, and is sufficient to reliably sample clinically significant prostate cancer foci under MRI-guidance.

Plexiform Neurofibromas in Children with Neurofibromatosis Type 1: Frequency and Associated Clinical Deficits

To define the frequency and clinical features of plexiform neurofibromas (PN) in children with neurofibromatosis type 1. Sixty-five children received whole-body magnetic resonance imaging (MRI) and clinical-neurologic examination. Tumor sizes were calculated volumetrically with the program MedX v3.42. χ(2) test, Fisher exact test, t test, and Spearman rank correlation were used for statistical analysis. Seventy-three tumors were detected in 37 of these 65 children. The mean volume of the tumors was 145.4 mL or 4.8 mL/kg body weight. Eighteen of the 73 PNs caused clinical deficits in 17 children, and the other 56 PNs in 20 children were asymptomatic. Symptomatic tumors were larger than asymptomatic ones (9.6 vs 3.3 mL/kg body weight; P = .01). However, in certain body regions, for example, the head, small tumors also caused clinical deficits. Ten of 18 children ≥11.5 years (median age of the 37 children with PNs) had symptomatic PNs compared with 7 of 19 who were <11.5 years (P = .25). PNs cause clinical deficits in young children. Early detection and regular MRI monitoring help to estimate growth and possible upcoming complications, and are thus beneficial for optimizing treatment and management.

Suivi par IRM de macrophages marqués et étude de la biotransformation cellulaire de l’agent de contraste

Objectives To monitor by magnetic resonance imaging (MRI) intra-carotid injection of labeled macrophages in an animal model of stroke, and to characterize the cellular biotransformation of iron nanoparticles using transmission electron microscopy (TEM). Materials and methods Male Sprague-Dawley rats were subjected to one hour transient occlusion of middle cerebral artery (MCAO). Immediately after reperfusion, four million macrophages magnetically labeled with iron oxide nanoparticles (USPIO) were administered into the (ipsilateral) carotid artery and MRI monitoring was performed on D0 and D1. Finally, to study iron oxide nanoparticles biotransformation, a TEM study combining conventional and electron diffraction approaches was performed on spleen sections of mice injected with contrast agent. Results and discussion Animals injected with labeled cells show a large number of hypointense spots in the ischemic lesion with a widespread and persistent distribution. The TEM results on D0 and D40 show the same maghemite structure of iron oxide nanoparticles heart. Conclusion MRI combined with in vitro cell labeling allows noninvasive and longitudinal cell monitoring. The intra-arterial administration provides a large number of cells to the lesion site. Finally, TEM study shows untransformed iron oxide particles on D40.

Tracing the Entrapped Air in Heterogeneous Soil by Means of Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) was used to study the process of infiltration in an undisturbed core of coarse sandy loam during a repeated ponded infiltration experiment (RPI), in which the first infiltration was conducted into a naturally dry sample and the second infiltration into a wet sample. The primary aim was to assess the change in distribution of entrapped air in the undisturbed soil sample and its influence on steady‐state flow rates. The RPI experiment was conducted on a sample 8.9 cm in diameter and 8.4 cm high. Concurrently with the MRI monitoring, pressure heads and fluxes were measured. Multiple‐slice maps of longitudinal relaxation time (T1), which is a parameter related to the surface/volume ratio, and proton density (M0), related to the water content, covered almost the entire volume of the sample. The T1 mapping was conducted during four stages of the experiment: steady‐state flow of the first (I1) and second (I2) infiltrations and the equilibrium stage after drainage of the sample (Stages D1 and D2). During I1 and I2, the highest values of M0 and T1 were detected in the upper 3 cm of the sample, which is in good agreement with findings of computer tomography showing lower sample density and higher porosity in this region. The drop in the quasi‐steady‐state flow rate that was observed between the I1 and I2 runs corresponded to the decline in T1 and M0 in the upper 4 cm of the sample. The decrease in T1 indicates replacement of water in large pores with trapped air, while a lower M0 signifies a general decrease of water content in the affected areas.

A Hierarchy of Self-Renewing Tumor-Initiating Cell Types in Glioblastoma

The neural stem cell marker CD133 is reported to identify cells within glioblastoma (GBM) that can initiate neurosphere growth and tumor formation; however, instances of CD133(-) cells exhibiting similar properties have also been reported. Here, we show that some PTEN-deficient GBM tumors produce a series of CD133(+) and CD133(-) self-renewing tumor-initiating cell types and provide evidence that these cell types constitute a lineage hierarchy. Our results show that the capacities for self-renewal and tumor initiation in GBM need not be restricted to a uniform population of stemlike cells, but can be shared by a lineage of self-renewing cell types expressing a range of markers of forebrain lineage.

Highly soluble multifunctional MnO nanoparticles for simultaneous optical and MRI imaging and cancer treatment using photodynamic therapy

Superparamagnetic MnO nanoparticles were functionalized using a hydrophilic ligand containing protoporphyrin IX as photosensitizer. By virtue of their magnetic properties these nanoparticles may serve as contrast enhancing agents for magnetic resonance imaging (MRI), while the fluorescent target ligand protoporphyrin IX allows simultaneous tumor detection and treatment by photodynamic therapy (PDT). Caki-1 cells were incubated with these nanoparticles. Subsequent exposure to UV light lead to cell apoptosis due to photoactivation of the photosensitizer conjugated to the nanoparticles. This method offers great diagnostic potential for highly proliferative tissues, including tumors. In addition, it is an efficient platform that combines the advantages of a biocompatible photosensitizer with the possibility for MRI monitoring due to the magnetic properties of the highly soluble functionalized manganese oxide nanoparticles.

MRI monitoring of lesions created at temperature below the boiling point and of lesions created above the boiling point using high intensity focused ultrasound

Magnetic Resonance Imaging (MRI) was utilized to monitor lesions created at temperature below the boiling point and lesions created at temperature above the boiling point using High Intensity Focused Ultrasound (HIFU) in freshly excised kidney, liver and brain and in vivo rabbit kidney and brain. T2-weighted fast spin echo (FSE) was proven as an excellent MRI sequence that can detect lesions with temperature above the boiling point in kidney. This advantage is attributed to the significant difference in signal intensity between the cavity and the thermal lesion. In liver the MRI sequence of Proton Density is recommended to detect lesions above boiling. In brain T1-W FSE was the optimum pulse sequence to detect lesions of either type. In order to monitor the temperature elevation during a HIFU exposure, T1-weighted fast spoiled gradient (FSPGR) was used. The shape of the focal temperature distribution was uniform with the absence of boiling, whereas with an exposure affected by boiling, the temperature distribution could be of irregular shape, demonstrating the drastic effects taking place during boiling. In order to confirm that boiling occurred, the temperature was estimated using the widely used method of Proton Resonance Frequency (PRF) shift.

Lymphomatous Meningitis: Early Diagnosis and Treatment

The incidence of central nervous system (CNS) metastases has increased steadily since 1999, likely because of the use of drugs with poor access to the CNS as well as the successful treatment of extraneural cancers, resulting in longer survival.Lymphomatous meningitis is a profoundly morbid and often fatal CNS metastasis that develops in at least 4%-8% of patients with non-Hodgkin lymphoma.Risk factors for lymphomatous meningitis include uncontrolled systemic and extranodal disease, testicular and parasinus tumors, and being younger than age 60. A high index of suspicion for the condition may result in earlier detection and improved outcome.Lymphomatous meningitis diagnostic methods include a thorough neurologic examination, magnetic resonance imaging (MRI), and multiple samplings of cerebrospinal fluid (CSF). Treatment regimens typically include radiation to areas of bulky disease or intrathecal chemotherapy.Available chemotherapeutic agents include methotrexate, cytarabine, and liposomal cytarabine.In addition to follow-up CSF and MRI monitoring, questioning patients and caregivers can provide insight into treatment response in terms of quality of life.Special care to avoid a nihilistic outlook in patients and clinicians is essential in treating patients with lymphomatous meningitis.

MRI Monitoring of Cartilage Repair in the Knee: A Review

Various treatment options for deep cartilage defects are presently available. The efficacy of bone marrow stimulation with microfracture, of mosaicplasty and of various autologous chondrocyte implantation (ACI) techniques has been subject to numerous studies recently. Magnetic resonance imaging (MRI) has gained a major role in the assessment of cartilage repair. The introduction of high-field MRI to clinical routine makes high resolution and three-dimensional imaging readily available. New quantitative MRI techniques that directly visualize the molecular structure of cartilage may further advance our understanding of cartilage repair. The clinical evaluation of cartilage repair tissue is a complex issue, and MR imaging will become increasingly important both in research and in clinical routine. This article reviews the clinical aspects of microfracture, mosaicplasty, and ACI and reports the recent technical advances that have improved MRI of cartilage. Morphological evaluation methods are recommended for each of the respective techniques. Finally, an overview of T2 mapping and delayed gadolinium-enhanced MR imaging of cartilage in cartilage repair is provided.

Differential Radiation Protection of Salivary Glands versus Tumor by Tempol with Accompanying Tissue Assessment of Tempol by Magnetic Resonance Imaging

The nitroxide free radical, Tempol, was evaluated for potential differential radiation protection of salivary glands and tumor using fractionated radiation. Mechanistic information was explored by monitoring the presence and bioreduction of Tempol in both tissues noninvasively by magnetic resonance imaging (MRI). Female C3H mice were immobilized using custom-made Lucite jigs for localized irradiation (five daily fractions) either to the oral cavity or tumor-bearing leg. Tempol (275 mg/kg) was administered (i.p.) 10 min before each radiation fraction. Salivary gland damage was assessed 8 weeks after radiation by measuring pilocarpine-mediated saliva output. Tumor growth was assessed by standard radiation regrowth methods. Dynamic T1-weighted magnetic resonance scans were acquired before and after Tempol injection using a 4.7T animal MRI instrument. Tempol treatment was found to protect salivary glands significantly against radiation damage (approximately 60% improvement); whereas no tumor protection was observed. Intracellular reduction of Tempol to the nonradioprotective hydroxylamine as assessed by MRI was 2-fold faster in tumor compared with salivary glands or muscle. Tempol provided salivary gland radioprotection and did not protect tumor, consistent with the hypothesis that differential radioprotection by Tempol resides in faster reduction to the nonradioprotective hydroxylamine in tumor compared with normal tissues. The unique paramagnetic properties of Tempol afforded noninvasive MRI monitoring of dynamic changes of Tempol levels in tissue to support the finding. These data support further development and consideration of Tempol for human clinical trials as a selective protector against radiation-induced salivary gland damage.