Ho-Taek Song - Academia.edu (original) (raw)
Papers by Ho-Taek Song
Journal of the Korean Society of Radiology, 2020
Magnetic resonance imaging (MRI) is an essential modality for the diagnosis of musculoskeletal sy... more 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.
Experimental neurobiology, 2018
Obesity-related metabolic disorders can affect not only systemic health but also brain function. ... more 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 visua...
Korean journal of radiology
To evaluate the feasibility of synthetic magnetic resonance imaging (MRI) compared to conventiona... more 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. 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. There was no statistically significant difference in image quality (= 0.90). Interobserver agreement (κ = 0.649- 0.981) and intersequ...
Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine, 2018
The purpose was to evaluate the feasibility of quantitative MRI T2 mapping based on the quantitat... more The purpose was to evaluate the feasibility of quantitative MRI T2 mapping based on the quantitative MRI (QRAPMASTER) sequence for the quantitative assessment of knee cartilage. The T2 values from the phantom study showed excellent correlation between the two techniques (r2 = 0.998). The cartilage T2 values exhibited strong correlations (r2 = 0.867-0.982). Quantitative MRI (qMRI) T2 mapping can be used as an alternative to multi-echo T2 mapping, with relatively short scan time.
Journal of the Korean Society of Radiology, 2011
The purpose of this study was to develop a nude mouse model of bone metastasis by performing intr... more The purpose of this study was to develop a nude mouse model of bone metastasis by performing intracardiac injection of breast cancer cells under ultrasonography guidance and we wanted to evaluate the development and the distribution of metastasis in vivo using micro-CT, MRI and bioluminescence imaging. Materials and Methods: Animal experiments were performed in 6-week-old female nude mice. The animals underwent left ventricular injection of 2×10 5 MDA-MB-231Bo-Luc cells. After injection of the tumor cells, serial bioluminescence imaging was performed for 7 weeks. The findings of micro-CT, MRI and the histology were correlated with the 'hot' lesions seen on the bioluminescence imaging. Results: Metastasis was found in 62.3% of the animals. Two weeks after intracardiac injection, metastasis to the brain, spine and femur was detected with bioluminescence imaging with an increasing intensity by week 7. Micro-CT scan confirmed multiple osteolytic lesions at the femur, spine and skull. MRI and the histology were able to show metastasis in the brain and extraskeletal metastasis around the femur. Conclusion: The intracardiac injection of cancer cells under ultrasonography guidance is a safe and highly reproducible method to produce bone metastasis in nude mice. This bone metastasis nude mouse model will be useful to study the mechanism of bone metastasis and to validate new therapeutics.
Investigative Magnetic Resonance Imaging, 2017
The discovery of the rapid dissolution dynamic nuclear polarization (DNP) technique has enabled r... more The discovery of the rapid dissolution dynamic nuclear polarization (DNP) technique has enabled real time imaging to reveal the kinetics of 13 C-labeled metabolites in vivo (1).
Neuropharmacology, Feb 1, 2017
The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2D... more The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IR...
![Research paper thumbnail of Alternating Acquisition Technique for Quantification ofin vitroHyperpolarized [1-13C] Pyruvate Metabolism](https://attachments.academia-assets.com/98878899/thumbnails/1.jpg)
](Investigative Magnetic Resonance Imaging, 2016
To develop a technique for quantifying the 13 C-metabolites by performing frequency-selective hyp... more To develop a technique for quantifying the 13 C-metabolites by performing frequency-selective hyperpolarized 13 C 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.
Experimental neurobiology, 2016
Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes... more 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-β-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 sen...
Investigative Magnetic Resonance Imaging, 2015
For a single time-point hyperpolarized 13 C magnetic resonance spectroscopy imaging (MRSI) of ani... more For a single time-point hyperpolarized 13 C 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 13 C 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%. Conclusion: Optimal scan timing to measure downstream metabolites using hyperpolarized 13 C MRSI can be determined by the proposed protocol-specific simulation approaches.
Magnetic resonance imaging, Jan 18, 2015
To develop a technique for frequency-selective hyperpolarized (13)C metabolic imaging in ultra-hi... more To develop a technique for frequency-selective hyperpolarized (13)C metabolic imaging in ultra-high field strength which exploits the broad spatial chemical shift displacement in providing spectral and spatial selectivity. The spatial chemical shift displacement caused by the slice-selection gradient was utilized in acquiring metabolite-selective images. Interleaved images of different metabolites were acquired by reversing the polarity of the slice-selection gradient at every repetition time, while using a low-bandwidth radio-frequency excitation pulse to alternatingly shift the displaced excitation bands outside the imaging subject. Demonstration of this technique is presented using (1)H phantom and in vivo mouse renal hyperpolarized (13)C imaging experiments with conventional chemical shift imaging and fast low-angle shot sequences. From phantom and in vivo mouse studies, the spectral selectivity of the proposed method is readily demonstrated using results of chemical shift spect...
Translational Oncology, 2013
The mechanism of action of arsenic trioxide (ATO) has been shown to be complex, influencing numer... more The mechanism of action of arsenic trioxide (ATO) has been shown to be complex, influencing numerous signal transduction pathways and resulting in a vast range of cellular effects. Among these mechanisms of action, ATO has been shown to cause acute vascular shutdown and massive tumor necrosis in a murine solid tumor model like vascular disrupting agent (VDA). However, relatively little is understood about this VDA-like property and its potential utility in developing clinical regimens. We focused on this VDA-like action of ATO. On the basis of the endothelial cell cytotoxicity assay and tubulin polymerization assay, we observed that higher concentrations and longer treatment with ATO reduced the level of αand β-tubulin and inhibited the polymerization of tubulin. The antitumor action and quantitative tumor perfusion studies were carried out with locally advanced murine CT26 colon carcinoma grown in female BALB/c mice. A single injection of ATO intraperitoneally displayed central necrosis of the tumor tissue by 24 hours. T1weighted dynamic contrast-enhanced magnetic resonance image revealed a significant decrease in tumor enhancement in the ATO-treated group. Similar to other VDAs, ATO treatment alone did not delay the progression of tumor growth; however, ATO treatment after injection of other cytotoxic agent (irinotecan) showed significant additive antitumor effect compared to control and irinotecan alone therapy. In summary, our data demonstrated that ATO acts as a VDA by means of microtubule depolymerization. It exhibits significant vascular shutdown activity in CT26 allograft model and enhances antitumor activity when used in combination with another cytotoxic chemotherapeutic agent.
Korean Journal of Radiology, 2005
We wanted to assess the role of the popliteal lymph nodes for differentiating rheumatoid arthriti... more We wanted to assess the role of the popliteal lymph nodes for differentiating rheumatoid arthritis (RA) from osteoarthritis (OA), and we also wanted to investigate the relationship between the popliteal lymph nodes and the inflamed synovial volume (ISV) by using contrast enhanced (CE), fat suppressed, three dimensional-fast spoiled gradient echo (3D-FSPGR) MR imaging. Materials and Methods: Contrast enhanced 3D-FSGPR MR imaging of 94 knees (21 with RA and 73 with OA) was analyzed. A lymph node was defined as being 'observed' if it could be seen in at least two planes of the three orthogonal reformatted planes. The number of observed lymph nodes, the mean of the smallest dimension of each lymph node and the existence of central fatty change were recorded. The OA group was graded according to the ISV calculated by a segmentation method: grade I was < 20 cm 3 ; grade II ranged from 20 cm 3 to 40 cm 3 ; and grade III was > 40 cm 3. Statistical analysis of the number and the mean size of the popliteal lymph nodes among the four groups (the RA group and the grade I-III OA groups) was performed. Results: The prevalence of the observed popliteal lymph nodes was significantly different between all the OA groups or between the grade III OA group and the RA group (p < 0.0001, 0.0001, respectively). The popliteal lymph node was observed in 32 out of 73 OA cases, whereas it was visible in all of the 21 RA cases. The number (mean standard deviation) of lymph nodes in the grade I OA group, the grade II OA group, the grade III OA group and the RA group was 1.2 0.4, 1.2 0.4, 1.3 0.5, and 2.7 1.1, respectively. The mean size (mean standard deviation) of the lymph nodes was 3.8 1.0 mm, 3.6 1.1 mm, 4.1 0.8 mm, and 5.4 1.3 mm, respectively. The incidence of central fatty changes was significantly lower in the RA group than in all the OA groups and the grade III OA group. When differentiating RA from OA, and when the differentiation was confined to the RA group and grade III OA group, respectively, the criteria of the number of lymph nodes, their size, their central fatty change and a combination of all these three criteria showed statistical significance (Az values for the former were 0.869, 0.847, 0.776, and 0.942; Az values for the latter were 0.855, 0.799, 0.712, and 0.916). The number and mean size of the lymph nodes correlated with the ISVs (r = 0.49, p < 0.001; 0.50, 0.001, respectively). Conclusion: The number, size and central fatty changes in the popliteal lymph nodes observed on the MR images might serve as simple and useful markers in differentiating RA disease from OA disease. These markers would be particular helpful in cases of severe synovial enhancement where the ISVs of both RA and OA overlap. The number and mean size of the lymph nodes also correlated well with the ISV.
Journal of the Korean Medical Association, 2009
M agnetic resonance (MR) imaging has been widely used in the clinic because of the benefit of hig... more M agnetic 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.
Korean Journal of Radiology, 2011
Objective: To investigate the correlation between quantitative dynamic contrast enhanced magnetic... more 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 10 6 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 (K trans , 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 K trans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, K trans and Kep were found to have an inverse relationship with MVD (r =-0.61, p = 0.06 in K trans ; 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, K trans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.
Yonsei Medical Journal, 2012
The purpose of this study was to investigate the predictability of pretreatment values including ... more The purpose of this study was to investigate the predictability of pretreatment values including Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) derived parameters (K trans , Kep and Ve), early changes in parameters (K trans , tumor volume), and heterogeneity (standard deviation of K trans) 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 (K trans , Kep and Ve) were calculated based on the Tofts model. Early changes in K trans , standard deviation (SD) of K trans , and tumor volume were also calculated. Tumor responses were evaluated based on histology. With a cutoff 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 K trans 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 K trans 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 K trans and showed an early reduction in K trans , demonstrating a more homogenous distribution.
The American journal of case reports, 2013
Male, 59 FINAL DIAGNOSIS: Xanthogranulomatous osteomyelitis Symptoms: Painful swelling in the wri... more Male, 59 FINAL DIAGNOSIS: Xanthogranulomatous osteomyelitis Symptoms: Painful swelling in the wrist Medication: Drug history of antifulgal agents Clinical Procedure: Excisional biopsy Specialty: Radiology. Rare disease. Xanthogranulomatous inflammation is a chronic inflammatory disease in which bone involvement is extremely rare. Bone involvement of xanthogranulomatous inflammation, termed xanthogranulomatous osteomyelitis (XO), often presents as a mass-like lesion extending to adjacent structures, which can mimic infiltrative carcinoma. We present a case of XO in the ulna, which mimicked a neoplasm. A 59-year-old man presented with a 2-month history of painful swelling in the right wrist. Plain radiography and CT showed an osteolytic lesion at the distal ulna. MRI revealed a soft-tissue mass with lobulated margins and contrast enhancement. Intense uptake in bone scan and PET suggested malignancy. An excisional biopsy from the representative area resulted in a pathology diagnosis of...
PLoS ONE, 2013
KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The an... more KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The anti-cancer mechanism of KML001 involves cancer cell destruction due to DNA damage at the telomeres of cancer cell chromosomes. In this study, we assessed the vascular disrupting properties of KML001 and investigated whether KML001 as VDA is able to increase antitumor activity in irinotecan combined treatment. We used a murine model of the CT26 colon carcinoma cell line. CT26 isograft mice treated intraperitoneally with 10 mg/kg KML001 displayed extensive central necrosis of tumor by 24 h. The vascular disrupting effects of KML001 were assessed by dynamic contrast enhanced magnetic resonance imaging. Gadopentetic acid-diethylene triaminepentaacetic acid contrast enhancement was markedly decreased in KML001-treated mice one day after treatment, whereas persistently high signal enhancement was observed in mice injected with saline. Rate constant K ep value representing capillary permeability was significantly decreased (p,0.05) in mice treated with KML001. Cytoskeletal changes of human umbilical vein endothelial cells (HUVECs) treated with 10 uM KML001 were assessed by immune blotting and confocal imaging. KML001 degraded tubulin protein in HUVECs, which may be related to vascular disrupting properties of KML001. Finally, in the mouse CT26 isograft model, KML001 combined with irinotecan significantly delayed tumor growth as compared to control and irinotecan alone. These results suggest that KML001 is a novel vascular disrupting agent, which exhibits significant vascular shutdown activity and enhances anti-tumor activity in combination with chemotherapy. These data further suggest an avenue for effective combination therapy in treating solid tumors.
NMR in Biomedicine, 2010
This study uses quantitative T2* imaging to track ferumoxides-protamine sulfate (FEPro) labeled M... more This study uses quantitative T2* imaging to track ferumoxides-protamine sulfate (FEPro) labeled MDA-MB-231BRL human breast cancer cells (231BRL) that metastasize to the nude rat brain. Four cohorts of nude rats were intracardiac (IC) injected with either FEPro labeled, unlabeled, TRIAL treated (to induce apoptosis) 231BRL cells or saline in order to develop metastatic breast cancer in the brain. The rat heads were imaged serially over 3-4 weeks using a gradient multi-echo and turbo spin echo pulse sequences at 3 Tesla with a solenoid receive only 4cm diameter coil. Quantitative T 2 * maps of whole brain were obtained by applying single exponential fitting to the signal intensity of T 2 * images and the distribution of T 2 * values in brain voxels were calculated. MRI findings were correlated with Prussian blue (PB) stain and immunohistochemical stain for iron in breast cancer and macrophages. Quantiative analysis of T 2 * from the brain voxels demonstrated a significant shift to lower values following IC injection of FEPro labeled 231BRL cells as compared to animals that received unlabeled cells or apoptotic cells or saline. Quartile analysis based on the T 2 * distribution obtained from brain voxels demonstrated significant differences (p<0.0083) in number of voxels with T 2 * values between 10-35 (Q1), 36-60 (Q2) and 61-86 (Q3) milliseconds from day 1 to 3 weeks post infusion of labeled 231BRL cells compared to baseline scans. There was no significant differences in the distribution of T 2 * obtained from serial MRI in rats receiving unlabeled or TRIAL treated cells or saline. Histological analysis demonstrated isolated PB positive breast cancer cells scattered in brains of rats that received labeled cells compared to animals that received unlabeled or apoptotic cells. Quantitative T 2 * analysis of FEPro labeled metastasized cancer cells was possible even after the hypointense voxels are no longer visible on T 2 *-weighted images.
Journal of the Korean Society of Radiology, 2020
Magnetic resonance imaging (MRI) is an essential modality for the diagnosis of musculoskeletal sy... more 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.
Experimental neurobiology, 2018
Obesity-related metabolic disorders can affect not only systemic health but also brain function. ... more 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 visua...
Korean journal of radiology
To evaluate the feasibility of synthetic magnetic resonance imaging (MRI) compared to conventiona... more 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. 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. There was no statistically significant difference in image quality (= 0.90). Interobserver agreement (κ = 0.649- 0.981) and intersequ...
Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine, 2018
The purpose was to evaluate the feasibility of quantitative MRI T2 mapping based on the quantitat... more The purpose was to evaluate the feasibility of quantitative MRI T2 mapping based on the quantitative MRI (QRAPMASTER) sequence for the quantitative assessment of knee cartilage. The T2 values from the phantom study showed excellent correlation between the two techniques (r2 = 0.998). The cartilage T2 values exhibited strong correlations (r2 = 0.867-0.982). Quantitative MRI (qMRI) T2 mapping can be used as an alternative to multi-echo T2 mapping, with relatively short scan time.
Journal of the Korean Society of Radiology, 2011
The purpose of this study was to develop a nude mouse model of bone metastasis by performing intr... more The purpose of this study was to develop a nude mouse model of bone metastasis by performing intracardiac injection of breast cancer cells under ultrasonography guidance and we wanted to evaluate the development and the distribution of metastasis in vivo using micro-CT, MRI and bioluminescence imaging. Materials and Methods: Animal experiments were performed in 6-week-old female nude mice. The animals underwent left ventricular injection of 2×10 5 MDA-MB-231Bo-Luc cells. After injection of the tumor cells, serial bioluminescence imaging was performed for 7 weeks. The findings of micro-CT, MRI and the histology were correlated with the 'hot' lesions seen on the bioluminescence imaging. Results: Metastasis was found in 62.3% of the animals. Two weeks after intracardiac injection, metastasis to the brain, spine and femur was detected with bioluminescence imaging with an increasing intensity by week 7. Micro-CT scan confirmed multiple osteolytic lesions at the femur, spine and skull. MRI and the histology were able to show metastasis in the brain and extraskeletal metastasis around the femur. Conclusion: The intracardiac injection of cancer cells under ultrasonography guidance is a safe and highly reproducible method to produce bone metastasis in nude mice. This bone metastasis nude mouse model will be useful to study the mechanism of bone metastasis and to validate new therapeutics.
Investigative Magnetic Resonance Imaging, 2017
The discovery of the rapid dissolution dynamic nuclear polarization (DNP) technique has enabled r... more The discovery of the rapid dissolution dynamic nuclear polarization (DNP) technique has enabled real time imaging to reveal the kinetics of 13 C-labeled metabolites in vivo (1).
Neuropharmacology, Feb 1, 2017
The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2D... more The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IR...
Investigative Magnetic Resonance Imaging, 2016
To develop a technique for quantifying the 13 C-metabolites by performing frequency-selective hyp... more To develop a technique for quantifying the 13 C-metabolites by performing frequency-selective hyperpolarized 13 C 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.
Experimental neurobiology, 2016
Neuronal senescence caused by diabetic neuropathy is considered a common complication of diabetes... more 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-β-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 sen...
Investigative Magnetic Resonance Imaging, 2015
For a single time-point hyperpolarized 13 C magnetic resonance spectroscopy imaging (MRSI) of ani... more For a single time-point hyperpolarized 13 C 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 13 C 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%. Conclusion: Optimal scan timing to measure downstream metabolites using hyperpolarized 13 C MRSI can be determined by the proposed protocol-specific simulation approaches.
Magnetic resonance imaging, Jan 18, 2015
To develop a technique for frequency-selective hyperpolarized (13)C metabolic imaging in ultra-hi... more To develop a technique for frequency-selective hyperpolarized (13)C metabolic imaging in ultra-high field strength which exploits the broad spatial chemical shift displacement in providing spectral and spatial selectivity. The spatial chemical shift displacement caused by the slice-selection gradient was utilized in acquiring metabolite-selective images. Interleaved images of different metabolites were acquired by reversing the polarity of the slice-selection gradient at every repetition time, while using a low-bandwidth radio-frequency excitation pulse to alternatingly shift the displaced excitation bands outside the imaging subject. Demonstration of this technique is presented using (1)H phantom and in vivo mouse renal hyperpolarized (13)C imaging experiments with conventional chemical shift imaging and fast low-angle shot sequences. From phantom and in vivo mouse studies, the spectral selectivity of the proposed method is readily demonstrated using results of chemical shift spect...
Translational Oncology, 2013
The mechanism of action of arsenic trioxide (ATO) has been shown to be complex, influencing numer... more The mechanism of action of arsenic trioxide (ATO) has been shown to be complex, influencing numerous signal transduction pathways and resulting in a vast range of cellular effects. Among these mechanisms of action, ATO has been shown to cause acute vascular shutdown and massive tumor necrosis in a murine solid tumor model like vascular disrupting agent (VDA). However, relatively little is understood about this VDA-like property and its potential utility in developing clinical regimens. We focused on this VDA-like action of ATO. On the basis of the endothelial cell cytotoxicity assay and tubulin polymerization assay, we observed that higher concentrations and longer treatment with ATO reduced the level of αand β-tubulin and inhibited the polymerization of tubulin. The antitumor action and quantitative tumor perfusion studies were carried out with locally advanced murine CT26 colon carcinoma grown in female BALB/c mice. A single injection of ATO intraperitoneally displayed central necrosis of the tumor tissue by 24 hours. T1weighted dynamic contrast-enhanced magnetic resonance image revealed a significant decrease in tumor enhancement in the ATO-treated group. Similar to other VDAs, ATO treatment alone did not delay the progression of tumor growth; however, ATO treatment after injection of other cytotoxic agent (irinotecan) showed significant additive antitumor effect compared to control and irinotecan alone therapy. In summary, our data demonstrated that ATO acts as a VDA by means of microtubule depolymerization. It exhibits significant vascular shutdown activity in CT26 allograft model and enhances antitumor activity when used in combination with another cytotoxic chemotherapeutic agent.
Korean Journal of Radiology, 2005
We wanted to assess the role of the popliteal lymph nodes for differentiating rheumatoid arthriti... more We wanted to assess the role of the popliteal lymph nodes for differentiating rheumatoid arthritis (RA) from osteoarthritis (OA), and we also wanted to investigate the relationship between the popliteal lymph nodes and the inflamed synovial volume (ISV) by using contrast enhanced (CE), fat suppressed, three dimensional-fast spoiled gradient echo (3D-FSPGR) MR imaging. Materials and Methods: Contrast enhanced 3D-FSGPR MR imaging of 94 knees (21 with RA and 73 with OA) was analyzed. A lymph node was defined as being 'observed' if it could be seen in at least two planes of the three orthogonal reformatted planes. The number of observed lymph nodes, the mean of the smallest dimension of each lymph node and the existence of central fatty change were recorded. The OA group was graded according to the ISV calculated by a segmentation method: grade I was < 20 cm 3 ; grade II ranged from 20 cm 3 to 40 cm 3 ; and grade III was > 40 cm 3. Statistical analysis of the number and the mean size of the popliteal lymph nodes among the four groups (the RA group and the grade I-III OA groups) was performed. Results: The prevalence of the observed popliteal lymph nodes was significantly different between all the OA groups or between the grade III OA group and the RA group (p < 0.0001, 0.0001, respectively). The popliteal lymph node was observed in 32 out of 73 OA cases, whereas it was visible in all of the 21 RA cases. The number (mean standard deviation) of lymph nodes in the grade I OA group, the grade II OA group, the grade III OA group and the RA group was 1.2 0.4, 1.2 0.4, 1.3 0.5, and 2.7 1.1, respectively. The mean size (mean standard deviation) of the lymph nodes was 3.8 1.0 mm, 3.6 1.1 mm, 4.1 0.8 mm, and 5.4 1.3 mm, respectively. The incidence of central fatty changes was significantly lower in the RA group than in all the OA groups and the grade III OA group. When differentiating RA from OA, and when the differentiation was confined to the RA group and grade III OA group, respectively, the criteria of the number of lymph nodes, their size, their central fatty change and a combination of all these three criteria showed statistical significance (Az values for the former were 0.869, 0.847, 0.776, and 0.942; Az values for the latter were 0.855, 0.799, 0.712, and 0.916). The number and mean size of the lymph nodes correlated with the ISVs (r = 0.49, p < 0.001; 0.50, 0.001, respectively). Conclusion: The number, size and central fatty changes in the popliteal lymph nodes observed on the MR images might serve as simple and useful markers in differentiating RA disease from OA disease. These markers would be particular helpful in cases of severe synovial enhancement where the ISVs of both RA and OA overlap. The number and mean size of the lymph nodes also correlated well with the ISV.
Journal of the Korean Medical Association, 2009
M agnetic resonance (MR) imaging has been widely used in the clinic because of the benefit of hig... more M agnetic 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.
Korean Journal of Radiology, 2011
Objective: To investigate the correlation between quantitative dynamic contrast enhanced magnetic... more 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 10 6 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 (K trans , 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 K trans and Kep that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, K trans and Kep were found to have an inverse relationship with MVD (r =-0.61, p = 0.06 in K trans ; 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, K trans and Kep tend to have a reverse correlation with MVD in this colon cancer mouse model.
Yonsei Medical Journal, 2012
The purpose of this study was to investigate the predictability of pretreatment values including ... more The purpose of this study was to investigate the predictability of pretreatment values including Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) derived parameters (K trans , Kep and Ve), early changes in parameters (K trans , tumor volume), and heterogeneity (standard deviation of K trans) 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 (K trans , Kep and Ve) were calculated based on the Tofts model. Early changes in K trans , standard deviation (SD) of K trans , and tumor volume were also calculated. Tumor responses were evaluated based on histology. With a cutoff 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 K trans 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 K trans 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 K trans and showed an early reduction in K trans , demonstrating a more homogenous distribution.
The American journal of case reports, 2013
Male, 59 FINAL DIAGNOSIS: Xanthogranulomatous osteomyelitis Symptoms: Painful swelling in the wri... more Male, 59 FINAL DIAGNOSIS: Xanthogranulomatous osteomyelitis Symptoms: Painful swelling in the wrist Medication: Drug history of antifulgal agents Clinical Procedure: Excisional biopsy Specialty: Radiology. Rare disease. Xanthogranulomatous inflammation is a chronic inflammatory disease in which bone involvement is extremely rare. Bone involvement of xanthogranulomatous inflammation, termed xanthogranulomatous osteomyelitis (XO), often presents as a mass-like lesion extending to adjacent structures, which can mimic infiltrative carcinoma. We present a case of XO in the ulna, which mimicked a neoplasm. A 59-year-old man presented with a 2-month history of painful swelling in the right wrist. Plain radiography and CT showed an osteolytic lesion at the distal ulna. MRI revealed a soft-tissue mass with lobulated margins and contrast enhancement. Intense uptake in bone scan and PET suggested malignancy. An excisional biopsy from the representative area resulted in a pathology diagnosis of...
PLoS ONE, 2013
KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The an... more KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The anti-cancer mechanism of KML001 involves cancer cell destruction due to DNA damage at the telomeres of cancer cell chromosomes. In this study, we assessed the vascular disrupting properties of KML001 and investigated whether KML001 as VDA is able to increase antitumor activity in irinotecan combined treatment. We used a murine model of the CT26 colon carcinoma cell line. CT26 isograft mice treated intraperitoneally with 10 mg/kg KML001 displayed extensive central necrosis of tumor by 24 h. The vascular disrupting effects of KML001 were assessed by dynamic contrast enhanced magnetic resonance imaging. Gadopentetic acid-diethylene triaminepentaacetic acid contrast enhancement was markedly decreased in KML001-treated mice one day after treatment, whereas persistently high signal enhancement was observed in mice injected with saline. Rate constant K ep value representing capillary permeability was significantly decreased (p,0.05) in mice treated with KML001. Cytoskeletal changes of human umbilical vein endothelial cells (HUVECs) treated with 10 uM KML001 were assessed by immune blotting and confocal imaging. KML001 degraded tubulin protein in HUVECs, which may be related to vascular disrupting properties of KML001. Finally, in the mouse CT26 isograft model, KML001 combined with irinotecan significantly delayed tumor growth as compared to control and irinotecan alone. These results suggest that KML001 is a novel vascular disrupting agent, which exhibits significant vascular shutdown activity and enhances anti-tumor activity in combination with chemotherapy. These data further suggest an avenue for effective combination therapy in treating solid tumors.
NMR in Biomedicine, 2010
This study uses quantitative T2* imaging to track ferumoxides-protamine sulfate (FEPro) labeled M... more This study uses quantitative T2* imaging to track ferumoxides-protamine sulfate (FEPro) labeled MDA-MB-231BRL human breast cancer cells (231BRL) that metastasize to the nude rat brain. Four cohorts of nude rats were intracardiac (IC) injected with either FEPro labeled, unlabeled, TRIAL treated (to induce apoptosis) 231BRL cells or saline in order to develop metastatic breast cancer in the brain. The rat heads were imaged serially over 3-4 weeks using a gradient multi-echo and turbo spin echo pulse sequences at 3 Tesla with a solenoid receive only 4cm diameter coil. Quantitative T 2 * maps of whole brain were obtained by applying single exponential fitting to the signal intensity of T 2 * images and the distribution of T 2 * values in brain voxels were calculated. MRI findings were correlated with Prussian blue (PB) stain and immunohistochemical stain for iron in breast cancer and macrophages. Quantiative analysis of T 2 * from the brain voxels demonstrated a significant shift to lower values following IC injection of FEPro labeled 231BRL cells as compared to animals that received unlabeled cells or apoptotic cells or saline. Quartile analysis based on the T 2 * distribution obtained from brain voxels demonstrated significant differences (p<0.0083) in number of voxels with T 2 * values between 10-35 (Q1), 36-60 (Q2) and 61-86 (Q3) milliseconds from day 1 to 3 weeks post infusion of labeled 231BRL cells compared to baseline scans. There was no significant differences in the distribution of T 2 * obtained from serial MRI in rats receiving unlabeled or TRIAL treated cells or saline. Histological analysis demonstrated isolated PB positive breast cancer cells scattered in brains of rats that received labeled cells compared to animals that received unlabeled or apoptotic cells. Quantitative T 2 * analysis of FEPro labeled metastasized cancer cells was possible even after the hypointense voxels are no longer visible on T 2 *-weighted images.