Hyperpolarized 1- 13Cpyruvate Magnetic Resonance Spectroscopy Shows That Agmatine Increased Lactate Production in the Brain of Type 2 Diabetic Mice

Purpose@#Type 2 diabetes mellitus (T2DM) is associated with a 2-fold increased risk of developing Alzheimer’s disease. In earlier research, agmatine has been demonstrated to alleviate diabetes symptoms and increase cognitive performance. However, it is unclear whether the improvement of cognitive function is attributable to the reduction of diabetic symptoms or its direct influence on brain metabolism. Using hyperpolarized (HP) [1- 13C]pyruvate magnetic resonance spectroscopy (MRS), this study intends to evaluate the influence of agmatine on brain metabolism. @*Materials and Methods@#ICR mice were fed a high-fat diet and injected with streptozotocin to develop a T2DM animal model. During a 2-week period, T2DM mice were treated with normal saline or 100 mg/kg of agmatine, and brain HP [1- 13C]pyruvate MRS was performed. The effect of agmatine on lactate generation and NADH/NAD+ redox state was investigated using C6 and neuro-2a (N2a) cells. @*Results@#As a perfusion marker, the total 13C signals in the brain of T2DM mice (p=0.07) and agmatine-treated mice (p<0.05) were reduced. The conversion constant (Kpl) from [1- 13C]pyruvate to [1- 13C]lactate was not distinguishable in the brains of T2DM mice but was significantly increased in the brains of agmatine-treated T2DM mice. Treating C6 and N2a cells with agmatine increased NADH/NAD+ ratio and lactate generation. @*Conclusion@#Agmatine influences the NADH/NAD+ redox state in the brains of T2DM mice, which may be connected with enhanced cognitive performance and increased conversion of HP [1- 13C]pyruvate to HP [1- 13C]lactate.

Artificial Intelligence and Deep Learning in Musculoskeletal Magnetic Resonance Imaging

The application of artificial intelligence (AI) and deep learning (DL) in radiology is rapidly evolving. AI in healthcare has benefits for image recognition, classification, and radiological workflows from a clinical perspective. Additionally, clinical triage AI can be applied to triage systems. This review aims to introduce the concept of DL and discuss its applications in the interpretation of magnetic resonance (MR) images and the DL-based reconstruction of accelerated MR images, with an emphasis on musculoskeletal radiology. The most recent developments and future directions are also discussed briefly.

Optimization of MRI Protocol for the Musculoskeletal System

Magnetic resonance imaging (MRI) is an essential modality for the diagnosis of musculoskeletal system defects because of its higher soft-tissue contrast and spatial resolution. With the recent development of MRI-related technology, faster imaging and various image plane reconstructions are possible, enabling better assessment of three-dimensional musculoskeletal anatomy and lesions. Furthermore, the image quality, diagnostic accuracy, and acquisition time depend on the MRI protocol used. Moreover, the protocol affects the efficiency of the MRI scanner. Therefore, it is important for a radiologist to optimize the MRI protocol. In this review, we will provide guidance on patient positioning; selection of the radiofrequency coil, pulse sequences, and imaging planes; and control of MRI parameters to help optimize the MRI protocol for the six major joints of the musculoskeletal system.

Assessment of Cognitive Impairment in a Mouse Model of High-Fat Diet-Induced Metabolic Stress with Touchscreen-Based Automated Battery System

Obesity-related metabolic disorders can affect not only systemic health but also brain function. Recent studies have elucidated that amyloid beta deposition cannot satisfactorily explain the development of Alzheimer's disease (AD) and that dysregulation of glucose metabolism is a critical factor for the sporadic onset of non-genetic AD. Identifying the pathophysiology of AD due to changes in brain metabolism is crucial; however, it is limited in measuring changes in brain cognitive function due to metabolic changes in animal models. The touchscreen-based automated battery system, which is more accurate and less invasive than conventional behavioral test tools, is used to assess the cognition of mice with dysregulated metabolism. This system was introduced in humans to evaluate cognitive function and was recently back-translated in monkeys and rodents. We used outbred ICR mice fed on high-fat diet (HFD) and performed the paired associates learning (PAL) test to detect their visual memory and new learning ability loss as well as to assess memory impairment. The behavioral performance of the HFD mice was weaker than that of normal mice in the training but was not significantly associated with motivation. In the PAL test, the average number of trials completed and proportion of correct touches was significantly lower in HFD mice than in normal diet-fed mice. Our results reveal that HFD-induced metabolic dysregulation has detrimental effects on operant learning according to the percentage of correct responses in PAL. These findings establish that HFD-induced metabolic stress may have an effect in accelerating AD-like pathogenesis.

Clinical Feasibility of Synthetic Magnetic Resonance Imaging in the Diagnosis of Internal Derangements of the Knee

OBJECTIVE: To evaluate the feasibility of synthetic magnetic resonance imaging (MRI) compared to conventional MRI for the diagnosis of internal derangements of the knee at 3T. MATERIALS AND METHODS: Following Institutional Review Board approval, image sets of conventional and synthetic MRI in 39 patients were included. Two musculoskeletal radiologists compared the image sets and qualitatively analyzed the images. Subjective image quality was assessed using a four-grade scale. Interobserver agreement and intersequence agreement between conventional and synthetic images for cartilage lesions, tears of the cruciate ligament, and tears of the meniscus were independently assessed using Kappa statistics. In patients who underwent arthroscopy (n = 8), the sensitivity, specificity, and accuracy for evaluated internal structures were calculated using arthroscopic findings as the gold standard. RESULTS: There was no statistically significant difference in image quality (p = 0.90). Interobserver agreement (κ = 0.649– 0.981) and intersequence agreement (κ = 0.794–0.938) were nearly perfect for all evaluated structures. The sensitivity, specificity, and accuracy for detecting cartilage lesions (sensitivity, 63.6% vs. 54.6–63.6%; specificity, 91.9% vs. 91.9%; accuracy, 83.3–85.4% vs. 83.3–85.4%) and tears of the cruciate ligament (sensitivity, specificity, accuracy, 100% vs. 100%) and meniscus (sensitivity, 50.0–62.5% vs. 62.5%; specificity, 100% vs. 87.5–100%; accuracy, 83.3–85.4% vs. 83.3–85.4%) were similar between the two MRI methods. CONCLUSION: Conventional and synthetic MRI showed substantial to almost perfect degree of agreement for the assessment of internal derangement of knee joints. Synthetic MRI may be feasible in the diagnosis of internal derangements of the knee.

Dual Component Analysis for In Vivo T₂* Decay of Hyperpolarized ¹³C Metabolites

PURPOSE: To investigate the exchange and redistribution of hyperpolarized ¹³C metabolites between different pools by temporally analyzing the relative fraction of dual T₂* components of hyperpolarized ¹³C metabolites. MATERIALS AND METHODS: A dual exponential decay analysis of T₂* is performed for [1-¹³C] pyruvate and [1-¹³C] lactate using nonspatially resolved dynamic ¹³C MR spectroscopy from mice brains with tumors (n = 3) and without (n = 4) tumors. The values of shorter and longer T₂* components are explored when fitted from averaged spectrum and temporal variations of their fractions. RESULTS: The T₂* values were not significantly different between the tumor and control groups, but the fraction of longer T₂* [1-¹³C] lactate components was more than 10% in the tumor group over that of the controls (P < 0.1). The fraction of shorter T₂* components of [1-¹³C] pyruvate showed an increasing tendency while that of the [1-¹³C] lactate was decreasing over time. The slopes of the changing fraction were steeper for the tumor group than the controls, especially for lactate (P < 0.01). In both pyruvate and lactate, the fraction of the shorter T₂* component was always greater than the longer T₂* component over time. CONCLUSIONS: The exchange and redistribution of pyruvate and lactate between different pools was investigated by dual component analysis of the free induction decay signal from hyperpolarized ¹³C experiments. Tumor and control groups showed differences in their fractions rather than the values of longer and shorter T₂* components. Fraction changing dynamics may provide an aspect for extravasation and membrane transport of pyruvate and lactate, and will be useful to determine the appropriate time window for acquisition of hyperpolarized ¹³C images.

Alternating Acquisition Technique for Quantification of in vitro Hyperpolarized 1-13C Pyruvate Metabolism

PURPOSE: To develop a technique for quantifying the 13C-metabolites by performing frequency-selective hyperpolarized 13C magnetic resonance spectroscopy (MRS) in vitro which combines simple spectrally-selective excitation with spectrally interleaved acquisition. METHODS: Numerical simulations were performed with varying noise level and K(p) values to compare the quantification accuracies of the proposed and the conventional methods. For in vitro experiments, a spectrally-selective excitation scheme was enabled by narrow-band radiofrequency (RF) excitation pulse implemented into a free-induction decay chemical shift imaging (FIDCSI) sequence. Experiments with LDH / NADH enzyme mixture were performed to validate the effectiveness of the proposed acquisition method. Also, a modified two-site exchange model was formulated for metabolism kinetics quantification with the proposed method. RESULTS: From the simulation results, significant increase of the lactate peak signal to noise ratio (PSNR) was observed. Also, the quantified K(p) value from the dynamic curves were more accurate in the case of the proposed acquisition method compared to the conventional non-selective excitation scheme. In vitro experiment results were in good agreement with the simulation results, also displaying increased PSNR for lactate. Fitting results using the modified two-site exchange model also showed expected results in agreement with the simulations. CONCLUSION: A method for accurate quantification of hyperpolarized pyruvate and the downstream product focused on in vitro experiment was described. By using a narrow-band RF excitation pulse with alternating acquisition, different resonances were selectively excited with a different flip angle for increased PSNR while the hyperpolarized magnetization of the substrate can be minimally perturbed with a low flip angle. Baseline signals from neighboring resonances can be effectively suppressed to accurately quantify the metabolism kinetics.

Agmatine Ameliorates High Glucose-Induced Neuronal Cell Senescence by Regulating the p21 and p53 Signaling

Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes mellitus. Neuronal senescence leads to the secretion of pro-inflammatory cytokines, the production of reactive oxygen species, and the alteration of cellular homeostasis. Agmatine, which is biosynthesized by arginine decarboxylation, has been reported in previous in vitro to exert a protective effect against various stresses. In present study, agmatine attenuated the cell death and the expression of pro-inflammatory cytokines such as IL-6, TNF-alpha and CCL2 in high glucose in vitro conditions. Moreover, the senescence associated-beta-galatosidase's activity in high glucose exposed neuronal cells was reduced by agmatine. Increased p21 and reduced p53 in high glucose conditioned cells were changed by agmatine. Ultimately, agmatine inhibits the neuronal cell senescence through the activation of p53 and the inhibition of p21. Here, we propose that agmatine may ameliorate neuronal cell senescence in hyperglycemia.

Comparison of Multi-Echo Dixon Methods with Volume Interpolated Breath-Hold Gradient Echo Magnetic Resonance Imaging in Fat-Signal Fraction Quantification of Paravertebral Muscle

OBJECTIVE: To assess whether multi-echo Dixon magnetic resonance (MR) imaging with simultaneous T2* estimation and correction yields more accurate fat-signal fraction (FF) measurement of the lumbar paravertebral muscles, in comparison with non-T2*-corrected two-echo Dixon or T2*-corrected three-echo Dixon, using the FF measurements from single-voxel MR spectroscopy as the reference standard. MATERIALS AND METHODS: Sixty patients with low back pain underwent MR imaging with a 1.5T scanner. FF mapping images automatically obtained using T2*-corrected Dixon technique with two (non-T2*-corrected), three, and six echoes, were compared with images from single-voxel MR spectroscopy at the paravertebral muscles on levels L4 through L5. FFs were measured directly by two radiologists, who independently drew the region of interest on the mapping images from the three sequences. RESULTS: A total of 117 spectroscopic measurements were performed either bilaterally (57 of 60 subjects) or unilaterally (3 of 60 subjects). The mean spectroscopic FF was 14.3 +/- 11.7% (range, 1.9-63.7%). Interobserver agreement was excellent between the two radiologists. Lin's concordance correlation between the spectroscopic findings and all the imaging-based FFs were statistically significant (p < 0.001). FFs obtained from the T2*-corrected six-echo Dixon sequences showed a significantly better concordance with the spectroscopic data, with its concordance correlation coefficient being 0.99 and 0.98 (p < 0.001), as compared with two- or three-echo methods. CONCLUSION: T2*-corrected six-echo Dixon sequence would be a better option than two- or three-echo methods for noninvasive quantification of lumbar muscle fat quantification.

Determination of Optimal Scan Time for the Measurement of Downstream Metabolites in Hyperpolarized 13C MRSI

PURPOSE: For a single time-point hyperpolarized 13C magnetic resonance spectroscopy imaging (MRSI) of animal models, scan-time window after injecting substrates is critical in terms of signal-to-noise ratio (SNR) of downstream metabolites. Prescans of time-resolved magnetic resonance spectroscopy (MRS) can be performed to determine the scan-time window. In this study, based on two-site exchange model, protocol-specific simulation approaches were developed for 13C MRSI and the optimal scan-time window was determined to maximize the SNR of downstream metabolites. MATERIALS AND METHODS: The arterial input function and conversion rate constant from injected substrates (pyruvate) to downstream metabolite (lactate) were precalibrated, based on pre-scans of time-resolved MRS. MRSI was simulated using twosite exchange model with considerations of scan parameters of MRSI. Optimal scantime window for mapping lactate was chosen from simulated lactate intensity maps. The performance was validated by multiple in vivo experiments of BALB/C nude mice with MDA-MB-231 breast tumor cells. As a comparison, MRSI were performed with other scan-time windows simply chosen from the lactate signal intensities of prescan time-resolved MRS. RESULTS: The optimal scan timing for our animal models was determined by simulation, and was found to be 15 s after injection of the pyruvate. Compared to the simple approach, we observed that the lactate peak signal to noise ratio (PSNR) was increased by 230%. CONCLUSIONS: Optimal scan timing to measure downstream metabolites using hyperpolarized 13C MRSI can be determined by the proposed protocol-specific simulation approaches.

Dual-Energy Computed Tomography Arthrography of the Shoulder Joint Using Virtual Monochromatic Spectral Imaging: Optimal Dose of Contrast Agent and Monochromatic Energy Level

OBJECTIVE: To optimize the dose of contrast agent and the level of energy for dual-energy computed tomography (DECT) arthrography of the shoulder joint and to evaluate the benefits of the optimized imaging protocol. MATERIALS AND METHODS: Dual-energy scans with monochromatic spectral imaging mode and conventional single energy scans were performed on a shoulder phantom with 10 concentrations from 0 to 210 mg/mL of iodinated contrast medium at intervals of 15 or 30 mg/mL. Image noise, tissue contrast, and beam hardening artifacts were assessed to determine the optimum dose of contrast agent and the level of monochromatic energy for DECT shoulder arthrography in terms of the lowest image noise and the least beam hardening artifacts while good tissue contrast was maintained. Material decomposition (MD) imaging for bone-iodine differentiation was qualitatively assessed. The optimized protocol was applied and evaluated in 23 patients. RESULTS: The optimal contrast dose and energy level were determined by the phantom study at 60 mg/mL and 72 keV, respectively. This optimized protocol for human study reduced the image noise and the beam-hardening artifacts by 35.9% and 44.5%, respectively. Bone-iodine differentiation by MD imaging was not affected by the iodine concentration or level of energy. CONCLUSION: Dual-energy scan with monochromatic spectral imaging mode results in reduced image noise and beam hardening artifacts.

Differentiation between Focal Malignant Marrow-Replacing Lesions and Benign Red Marrow Deposition of the Spine with T2*-Corrected Fat-Signal Fraction Map Using a Three-Echo Volume Interpolated Breath-Hold Gradient Echo Dixon Sequence

OBJECTIVE: To assess the feasibility of T2*-corrected fat-signal fraction (FF) map by using the three-echo volume interpolated breath-hold gradient echo (VIBE) Dixon sequence to differentiate between malignant marrow-replacing lesions and benign red marrow deposition of vertebrae. MATERIALS AND METHODS: We assessed 32 lesions from 32 patients who underwent magnetic resonance imaging after being referred for assessment of a known or possible vertebral marrow abnormality. The lesions were divided into 21 malignant marrow-replacing lesions and 11 benign red marrow depositions. Three sequences for the parameter measurements were obtained by using a 1.5-T MR imaging scanner as follows: three-echo VIBE Dixon sequence for FF; conventional T1-weighted imaging for the lesion-disc ratio (LDR); pre- and post-gadolinium enhanced fat-suppressed T1-weighted images for the contrast-enhancement ratio (CER). A region of interest was drawn for each lesion for parameter measurements. The areas under the curve (AUC) of the parameters and their sensitivities and specificities at the most ideal cutoff values from receiver operating characteristic curve analysis were obtained. AUC, sensitivity, and specificity were respectively compared between FF and CER. RESULTS: The AUCs of FF, LDR, and CER were 0.96, 0.80, and 0.72, respectively. In the comparison of diagnostic performance between the FF and CER, the FF showed a significantly larger AUC as compared to the CER (p = 0.030), although the difference of sensitivity (p = 0.157) and specificity (p = 0.157) were not significant. CONCLUSION: Fat-signal fraction measurement using T2*-corrected three-echo VIBE Dixon sequence is feasible and has a more accurate diagnostic performance, than the CER, in distinguishing benign red marrow deposition from malignant bone marrow-replacing lesions.

Four-Dimensional Real-Time Cine Images of Wrist Joint Kinematics Using Dual Source CT with Minimal Time Increment Scanning

PURPOSE: To validate the feasibility of real time kinematography with four-dimensional (4D) dynamic functional wrist joint imaging using dual source CT. MATERIALS AND METHODS: Two healthy volunteers performed radioulnar deviation and pronation-supination wrist motions for 10 s and 4 s per cycle in a dual source CT scanner. Scan and reconstruction protocols were set to optimize temporal resolution. Cine images of the reconstructed carpal bone of the moving wrist were recorded. The quality of the images and radiation dosage were evaluated. RESULTS: The 4D cine images obtained during 4 s and 10 s of radioulnar motion showed a smooth stream of movement with good quality and little noise or artifact. Images from the pronation-supination motion showed noise with a masked surface contour. The temporal resolution was optimized at 0.28 s. CONCLUSION: Using dual source CT, 4D cine images of in vivo kinematics of wrist joint movement were obtained and found to have a shorter scan time, improved temporal resolution and lower radiation dosages compared with those previously reported.

Characteristic MRI Findings of Spinal Metastases from Various Primary Cancers: Retrospective Study of Pathologically-Confirmed Cases

PURPOSE: The purpose of this study was to find and categorize the various magnetic resonance imaging (MRI) findings of spinal metastases that correlate with the type of primary cancer. MATERIALS AND METHODS: We retrospectively reviewed gadolinium-enhanced magnetic resonance images of 30 patients with 169 spinal metastatic lesions from lung cancer (n = 56), breast cancer (n = 29), colorectal cancer (n = 20), hepatocellular carcinoma (HCC) (n = 17), and stomach cancer (n = 47). The size, location, extent of invasion, signal intensity, margin, enhancement pattern, and osteoblastic or osteolytic characteristics of each metastatic tumor were analyzed. RESULTS: The metastatic lesions from HCC were larger than those from the other primary tumors (P < 0.05) except for colorectal cancer (P = 0.268). Well-defined metastatic tumor margins were more frequently seen in lung cancer and breast cancer (P < 0.01). All but HCC showed a tendency to invade the vertebral body rather than the posterior elements (P < 0.02). Colorectal cancer and HCC showed a tendency toward extraosseous invasion without statistical significance. HCC showed a characteristic enhancement pattern of 'worms-in-a-bag'. Rim enhancement with a sclerotic center was only seen in spinal metastases from stomach cancer. CONCLUSION: Despite many overlapping imaging features, spinal metastases of various primary tumors display some characteristic MRI findings that can help identify the primary cancer.

Quantitative Assessment and Ligament Traceability of Volume Isotropic Turbo Spin Echo Acquisition (VISTA) Ankle Magnetic Resonance Imaging: Fat Suppression versus without Fat Suppression

PURPOSE: To compare the image quality and ligament traceability in ankle images obtained using Volume Isotropic Turbo Spin Echo Acquisition (VISTA) MRI with and without fat suppression. MATERIALS AND METHODS: The signal-to-noise ratios (SNRs) in images from a phantom and from the ankle of a volunteer were compared. Ten ankles from 10 non-symptomatic volunteers were imaged for comparisons of contrast ratio (CR) and ligament traceability. All examinations were performed using VISTA sequences with and without fat suppression on a 3T MRI scanner. The SNRs were obtained from images with subjects and without subjects (noise-only). Contrast ratios from images of the 10 ankles were acquired between fluid and tendon (F-T), F-cartilage (C), F-ligament (L), fat (f)-T, f-C and f-L. Two musculoskeletal radiologists independently scored the traceability of 7 ligaments, in sagittal, axial and coronal images respectively, based on a 4-point scale (1 as not traceable through 4 as clearly traceable). The Wilcoxon signed-rank test was used to compare the CR. Fisher's exact test and Pearson's chi-squared test were used to compare the ligament traceability. RESULTS: The SNRs did not differ significantly between the two sequences except in bone marrow. VISTA SPAIR showed the higher CR only in F-T (p = 0.04), whereas VISTA showed higher CR in f-T (p = 0.005), f-C (p = 0.005) and f-L (p = 0.005). The calcaneofibular ligament traceability with VISTA was superior to that obtained with VISTA SPAIR (p < 0.05) in all planes. CONCLUSION: VISTA showed significant superiority to VISTA SPAIR in tracing CFL due to the superior CR between fat and ligament.

Determination of Optimal Imaging Mode for Ultrasonographic Detection of Subdermal Contraceptive Rods: Comparison of Spatial Compound, Conventional, and Tissue Harmonic Imaging Methods

OBJECTIVE: To determine which mode of ultrasonography (US), among the conventional, spatial compound, and tissue-harmonic methods, exhibits the best performance for the detection of Implanon(R) with respect to generation of posterior acoustic shadowing (PAS). MATERIALS AND METHODS: A total of 21 patients, referred for localization of impalpable Implanon(R), underwent US, using the three modes with default settings (i.e., wide focal zone). Representative transverse images of the rods, according to each mode for all patients, were obtained. The resulting 63 images were reviewed by four observers. The observers provided a confidence score for the presence of PAS, using a five-point scale ranging from 1 (definitely absent) to 5 (definitely present), with scores of 4 or 5 for PAS being considered as detection. The average scores of PAS, obtained from the three different modes for each observer, were compared using one-way repeated measure ANOVA. The detection rates were compared using a weighted least square method. RESULTS: Statistically, the tissue harmonic mode was significantly superior to the other two modes, when comparing the average scores of PAS for all observers (p < 0.00-1). The detection rate was also highest for the tissue harmonic mode (p < 0.001). CONCLUSION: Tissue harmonic mode in uS appears to be the most suitable in detecting subdermal contraceptive implant rods.

Quantitative Assessment of Tumor Responses after Radiation Therapy in a DLD-1 Colon Cancer Mouse Model Using Serial Dynamic Contrast-Enhanced Magnetic Resonance Imaging

PURPOSE: The purpose of this study was to investigate the predictability of pretreatment values including Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) derived parameters (Ktrans, Kep and Ve), early changes in parameters (Ktrans, tumor volume), and heterogeneity (standard deviation of Ktrans) for radiation therapy responses via a human colorectal cancer xenograft model. MATERIALS AND METHODS: A human colorectal cancer xenograft model with DLD-1 cancer cells was produced in the right hind limbs of five mice. Tumors were irradiated with 3 fractions of 3 Gy each for 3 weeks. Baseline and follow up DCE-MRI were performed. Quantitative parameters (Ktrans, Kep and Ve) were calculated based on the Tofts model. Early changes in Ktrans, standard deviation (SD) of Ktrans, and tumor volume were also calculated. Tumor responses were evaluated based on histology. With a cut-off value of 0.4 for necrotic factor, a comparison between good and poor responses was conducted. RESULTS: The good response group (mice #1 and 2) exhibited higher pretreatment Ktrans than the poor response group (mice #3, 4, and 5). The good response group tended to show lower pretreatment Kep, higher pretreatment Ve, and larger baseline tumor volume than the poor response group. All the mice in the good response group demonstrated marked reductions in Ktrans and SD value after the first radiation. All tumors showed increased volume after the first radiation therapy. CONCLUSION: The good response after radiation therapy group in the DLD-1 colon cancer xenograft nude mouse model exhibited a higher pretreatment Ktrans and showed an early reduction in Ktrans, demonstrating a more homogenous distribution.

Magnetic Resonance Arthrographic Dissection of Posterolateral Corner of the Knee: Revealing the Meniscofibular Ligament

PURPOSE: To evaluate meniscofibular ligament (MFibL) at the posterolateral corner of the knee joint on the magnetic resonance arthrography (MRA) with 70degrees knee flexion. MATERIALS AND METHODS: The MRA of the knee joint was performed at 70degrees knee flexion. Eighteen patients (19 knee joints) underwent scanning of sagittal, coronal, and axial fat-suppressed T1 weighted images (T1FS), and coronal fat-suppressed T2 weighted images. Sagittal three-dimensional (3D) gradient echo (GRE) images were also obtained. Retrospective review of 19 knee MRA studies was independently performed by two musculoskeletal radiologists. The statistical significance was proved by chi-square test. RESULTS: The MFibL ligament was optimally demonstrated on the far lateral sagittal 3D GRE and T1FS MRA images. The MFibL appeared as a curvilinear or straight hypointense band of variable thickness, extended from the posterolateral meniscus to upper anteromedial aspect of the fibular head. The MFibL was demonstrated with scale 2 (more than a half length of the ligament) by both reviewers in 73.68% (n=14/19) of the knee 3D GRE images and 89.47% (n=17/19) of the knee T1FS images. The visualization on T1FS and that on GRE were not statistically different from each other (p>0.05). The interobserver agreements were significantly good on both 3D GRE and T1FS images in detecting the ligament (kappa values, 0.642 and 0.683, respectively). CONCLUSION: The MFibL is well visualized on the far lateral sagittal MRA at 70degrees knee flexion, which could potentially be useful in recognizing structures in the posterolateral corner of the knee, including the MFibL.

Correlations of 3T DCE-MRI Quantitative Parameters with Microvessel Density in a Human-Colorectal-Cancer Xenograft Mouse Model

OBJECTIVE: To investigate the correlation between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters and microvascular density (MVD) in a human-colon-cancer xenograft mouse model using 3 Tesla MRI. MATERIALS AND METHODS: A human-colon-cancer xenograft model was produced by subcutaneously inoculating 1 x 106 DLD-1 human-colon-cancer cells into the right hind limbs of 10 mice. The tumors were allowed to grow for two weeks and then assessed using MRI. DCE-MRI was performed by tail vein injection of 0.3 mmol/kg of gadolinium. A region of interest (ROI) was drawn at the midpoints along the z-axes of the tumors, and a Tofts model analysis was performed. The quantitative parameters (Ktrans, Kep and Ve) from the whole transverse ROI and the hotspot ROI of the tumor were calculated. Immunohistochemical microvessel staining was performed and analyzed according to Weidner's criteria at the corresponding MRI sections. Additional Hematoxylin and Eosin staining was performed to evaluate tumor necrosis. The Mann-Whitney test and Spearman's rho correlation analysis were performed to prove the existence of a correlation between the quantitative parameters, necrosis, and MVD. RESULTS: Whole transverse ROI of the tumor showed no significant relationship between the MVD values and quantitative DCE-MRI parameters. In the hotspot ROI, there was a difference in MVD between low and high group of Ktrans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, Ktrans and Kep were found to have an inverse relationship with MVD (r = -0.61, p = 0.06 in Ktrans; r = -0.60, p = 0.07 in Kep). CONCLUSION: Quantitative analysis of T1-weighted DCE-MRI using hotspot ROI may provide a better histologic match than whole transverse section ROI. Within the hotspots, Ktrans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.

Cancer -Targeted MR Molecular Imaging

Magnetic resonance (MR) imaging has been widely used in the clinic because of the benefit of high spatial and temporal resolution, and the excellent anatomical tissue contrast. Cancer-targeted MR molecular imaging comprises 3 major components: a relevant molecular target which is specifically highly expressed on the membrane of the cancer cell; a target specific imaging probe which is composed of superparamagnetic iron oxide nanoparticle coreconjugated target specific ligand such as antibody, peptide, and molecules; MR imaging hardware and software which are sensitive to the imaging probe. Among the various molecular targets, HER2/neu receptor antibody, folic acid, and arginine-glycine-aspartic acid (RGD) are well known targeting ligands. The sensitivity of the cancer-targeted MR imaging is affected by the magnetic susceptibility of the T2 contrast agent, resolution of the image, targeting efficiency of the imaging probe, and image acquisition pulse sequence. Recently, successful cancer-targeted MR imaging with T1 contrast agent and cancer-specific molecular MR imaging using innate contrast of the cancer cell by chemical exchange phenomenon without using the imaging probe has been introduced. Cancer-targeted MR molecuar imaging is a robust diagnostic method to detect cancer at the cellular stage of the cancer development and it would help improve early detection rate of the cancer.