Comparison of T1 relaxation times in adipose tissue of severely obese patients and healthy lean subjects measured by 1.5 T MRI

Subcutaneous (SAT) and visceral adipose tissue (VAT) differ in composition, endocrine function and localization in the body. VAT is considered to play a role in the pathogenesis of insulin resistance, type 2 diabetes, fatty liver disease, and other obesity‐related disorders. It has been shown that the amount, distribution, and (cellular) composition of adipose tissue (AT) correlate well with metabolic conditions. In this study, T₁ relaxation times of AT were measured in severely obese subjects and compared with those of healthy lean controls. Here, we tested the hypothesis that T₁ relaxation times of AT differ between lean and obese individuals, but also between VAT and SAT as well as superficial (sSAT) and deep SAT (dSAT) in the same individual. Twenty severely obese subjects (BMI 41.4 ± 4.8 kg/m²) and ten healthy lean controls matched for age (BMI 21.5 ± 1.9 kg/m²) underwent MRI at 1.5 T using a single‐shot fast spin‐echo sequence (short‐tau inversion recovery) at six different inversion times (T_I range 100–1000 ms). T₁ relaxation times were computed for all subjects by fitting the T_I‐dependent MR signal intensities of user‐defined regions of interest in both SAT and VAT to a model function. T₁ times in sSAT and dSAT were only measured in obese patients. For both obese patients and controls, the T₁ times of SAT (275 ± 14 and 301 ± 12 ms) were significantly (p < 0.01) shorter than the respective values in VAT (294 ± 20 and 360 ± 35 ms). Obese subjects also showed significant (p < 0.01) T₁ differences between sSAT (268 ± 11 ms) and dSAT (281 ± 19 ms). More important, T₁ differences in both SAT and VAT were highly significant (p < 0.001) between obese patients and healthy subjects. The results of our pilot study suggest that T₁ relaxation times differ between severely obese patients and lean controls, and may potentially provide an additional means for the non‐invasive assessment of AT conditions and dysfunction. Copyright © 2014 John Wiley & Sons, Ltd.     

Characterizing human adipose tissue lipids by long echo time 1H‐MRS in vivo at 1.5 Tesla: validation by gas chromatography

The aim of this study was to investigate the use of ¹H‐MRS with various echo times to characterize subcutaneous human adipose tissue (SAT) triglyceride composition and to validate the findings with fatty acid (FA) analysis of SAT biopsies by gas chromatography (GC). ¹H‐MRS spectra were acquired with a 1.5 Tesla clinical imager from the SAT of 17 healthy volunteers, with 10 undergoing SAT biopsy. Spectra were localized with PRESS and a series of echo times; 30,50,80,135,200,300 and 540 ms were acquired with TR = 3000 ms. Prior knowledge from phantom measurements was used to construct AMARES fitting models for the lipid spectra. SAT FA composition were compared with serum lipid levels and subject characteristics in 17 subjects. Long TE (135,200 ms) spectra corresponded better with the GC data than short TE (30,50 ms) spectra. TE = 135 ms was found optimal for determining diallylic content (R = 0.952, p < 0.001) and TE = 200 ms was optimal for determining olefinic content (R = 0.800, p < 0.01). The improved performance of long TE spectra is a result of an improved baseline and better peak separation, due to J‐modulation and suppression of water. The peak position of the diallylic resonance correlated with the average double bond content of polyunsatured fatty acids with R = 0.899 (p < 0.005). The apparent T₂ of the methylene resonance displayed relatively small inter‐individual variation, 88.1 ± 1.1 ms (mean ± SD). The outer methyl triplet line of ω‐3 PUFA at 1.08 ppm could be readily detected and quantitated from spectra obtained at TE = 540. The ω‐3 resonance correlated with the ω‐3 content determined by GC with R = 0.737 (p < 0.05, n = 8). Age correlated significantly with SAT diallylic content (R = 0.569, p = 0.017, n = 17), but serum lipid levels showed no apparent relation to SAT FA composition. We conclude that long TE ¹H‐MRS provides a robust non‐invasive method for characterizing adipose tissue triglycerides in vivo. Copyright © 2010 John Wiley & Sons, Ltd.     

In vivo characterization of fatty acids in human adipose tissue using natural abundance 1H decoupled 13C MRS at 1.5 T: clinical applications to dietary therapy

Natural abundance proton-decoupled (13)C magnetic resonance spectroscopy was used to establish the in vivo lipid composition of normal adipose tissue and the corresponding effects of altered lipid diets. Experiments were performed on a standard 1.5 T clinical MR scanner using a double-tuned (1)H-(13)C coil. Peaks from double-bonded and methylene carbons were analyzed. Normal lipid composition was established in 20 control subjects. For comparison, five subjects on altered lipid diets were studied. Four subjects were on a fish oil supplement diet or predominantly seafood diet (polyunsaturated fatty acids), and one subject was on a Lorenzo's oil diet (monounsaturated fatty acids). Well-resolved (13)C spectra were obtained from the calf adipose tissue with a total acquisition time of 10 min. Model oil solutions were used to identify specific (13)C resonances. Subjects on lipid diets showed significantly elevated levels of monounsaturated and polyunsaturated fatty acids for Lorenzo's and fish oil diets, respectively. We conclude that (13)C MR spectroscopy can readily detect changes in lipid composition due to medium- and long-term therapeutic lipid diets. Since the examination is rapid, robust and noninvasive, opportunities arise for large clinical trials of preventive or therapeutic diets to be performed with (13)C MRS on a clinical MR scanner.     

Intra‐ and interindividual variability of fatty acid unsaturation in six different human adipose tissue compartments assessed by 1H‐MRS in vivo at 3 T

It is generally accepted that the amount and distribution of adipose tissue (AT) in the human body play an important role in the pathogenesis of metabolic diseases. In addition, metabolic effects of released saturated fatty acids (FAs) in blood are known to be more critical than those of unsaturated FAs. However, little is known about the variability in unsaturation of FAs in various AT compartments. The aim of this prospective study was the assessment of mono‐ and polyunsaturated FAs in various AT compartments by localized ¹H‐MRS in order to obtain insight into the intra‐ and interindividual variability. Associations of FA unsaturation with intrahepatic lipids (IHLs), insulin sensitivity and related AT volumes were analyzed. Fifty healthy Caucasians (36 male, 14 female) participated in this study. Spectroscopic examinations were performed in subcutaneous adipose tissue in the neck (SCAT_neck), abdominal deep subcutaneous adipose tissue (DSCAT), abdominal superficial subcutaneous adipose tissue (SSCAT), visceral adipose tissue (VAT), tibial bone marrow (BM) and subcutaneous adipose tissue of the lower leg (SCAT_calf) at 3 T. Unsaturated index (UI) was calculated by the ratio of olefinic and methyl resonances, polyunsaturated index (PUI) by the ratio of diallylic and methyl resonances. Volumes of AT compartments (by T₁‐weighted MRI) and IHL (single‐voxel STEAM) were assessed at 1.5 T, insulin sensitivity by an oral glucose tolerance test. UI was highest for SCAT_calf (0.622) and lowest for BM (0.527). Highest PUI was observed for SSCAT (0.108), lowest for BM (0.093). Significant intraindividual differences between UIs—but not PUIs—are present for most compartments. There is a non‐significant trend for higher UI in males but otherwise no correlation to anthropometric data (age, BMI). A significant negative correlation between UI and AT volume was observed for VAT but for none of the other compartments. Neither UIs nor PUIs show a relation with IHL; insulin sensitivity is significantly correlated to UI in BM (p < 0.01). Unsaturation indices in several distinct AT compartments are location dependent. Our cohort showed only moderate gender‐related differences, with a trend towards less unsaturated FAs (mainly PUI) in females. In BM, insulin resistant subjects are characterized by a higher UI compared with the insulin sensitive ones. Further studies in larger cohorts are necessary to gain further insight into unsaturation of AT.     

Effect of taxane‐based neoadjuvant chemotherapy on fibroglandular tissue volume and percent breast density in the contralateral normal breast evaluated by 3T MR

The aim of this study was to evaluate the change of breast density in the normal breast of patients receiving neoadjuvant chemotherapy (NAC). Forty‐four breast cancer patients were studied. MRI acquisition was performed before treatment (baseline), and 4 and 12 weeks after treatment. A computer‐algorithm‐based program was used to segment breast tissue and calculate breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) (the ratio of FV over BV × 100%). The reduction of FV and PD after treatment was compared with baseline using paired t‐tests with a Bonferroni–Holm correction. The association of density reduction with age was analyzed. FV and PD after NAC showed significant decreases compared with the baseline. FV was 110.0 ml (67.2, 189.8) (geometric mean (interquartile range)) at baseline, 104.3 ml (66.6, 164.4) after 4 weeks (p < 0.0001), and 94.7 ml (60.2, 144.4) after 12 weeks (comparison with baseline, p < 0.0001; comparison with 4 weeks, p = 0.016). PD was 11.2% (6.4, 22.4) at baseline, 10.6% (6.6, 20.3) after 4 weeks (p < 0.0001), and 9.7% (6.2, 17.9) after 12 weeks (comparison with baseline, p = 0.0001; comparison with 4 weeks, p = 0.018). Younger patients tended to show a higher density reduction, but overall correlation with age was only moderate (r = 0.28 for FV, p = 0.07, and r = 0.52 for PD, p = 0.0003). Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer‐aided algorithm based on non‐parametric non‐uniformity normalization (N3) and an adaptive fuzzy C‐means algorithm. Similar to doxorubicin and cyclophosphamide regimens, the taxane‐based NAC regimen also caused density atrophy in the normal breast and showed reduction in FV and PD. The effect of breast density reduction was age related and duration related. Copyright © 2013 John Wiley & Sons, Ltd.     

Validation of fast MR thermometry at 1.5 T with gradient-echo echo planar imaging sequences: phantom and clinical feasibility studies

The purpose of this work was to validate in phantom studies and demonstrate the clinical feasibility of MR proton resonance frequency thermometry at 1.5 T with segmented gradient-echo echo planar imaging (GRE-EPI) sequences during liver tumour radiofrequency (RF) ablation. Classical GRE acquisitions and segmented GRE-EPI acquisitions were performed at 1.5 T during simultaneous RF heating with an MR-compatible RF electrode placed in an agar gel phantom. Temperature increments were calculated and compared with four optical temperature probe measurements using Bland- Altman analysis. In a preliminary clinical feasibility study, the rapid GRE-EPI sequence (echo train length = 13) was used for MR temperature monitoring of RF ablation of liver tumours in three patient procedures. For phantom experiments, the Bland-Altman mean of differences between MR and optical probe temperature measurements was <0.4 degrees C, and the 95% limits of agreement value was <1.4 degrees C. For the in vivo studies, respiratory-triggered GRE-EPI acquisitions yielded a temperature accuracy of 1.3 +/- 0.4 degrees C (acquisition time = 0.6 s/image, spatial coverage of three slices/respiratory cycle). MR proton resonance frequency thermometry at 1.5 T yields precise and accurate measurements of temperature increment with both classical GRE and rapid GRE-EPI sequences. Rapid GRE-EPI sequences minimize intra-scan motion effects and can be used for MR thermometry during RF ablation in moving organs. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Validation of a fast method for quantification of intra‐abdominal and subcutaneous adipose tissue for large‐scale human studies

Central obesity is the hallmark of a number of non‐inheritable disorders. The advent of imaging techniques such as MRI has allowed for a fast and accurate assessment of body fat content and distribution. However, image analysis continues to be one of the major obstacles to the use of MRI in large‐scale studies. In this study we assess the validity of the recently proposed fat–muscle quantitation system (AMRA^TM Profiler) for the quantification of intra‐abdominal adipose tissue (IAAT) and abdominal subcutaneous adipose tissue (ASAT) from abdominal MR images. Abdominal MR images were acquired from 23 volunteers with a broad range of BMIs and analysed using sliceOmatic, the current gold‐standard, and the AMRA^TM Profiler based on a non‐rigid image registration of a library of segmented atlases. The results show that there was a highly significant correlation between the fat volumes generated by the two analysis methods, (Pearson correlation r = 0.97, p < 0.001), with the AMRA^TM Profiler analysis being significantly faster (~3 min) than the conventional sliceOmatic approach (~40 min). There was also excellent agreement between the methods for the quantification of IAAT (AMRA 4.73 ± 1.99 versus sliceOmatic 4.73 ± 1.75 l, p = 0.97). For the AMRA^TM Profiler analysis, the intra‐observer coefficient of variation was 1.6% for IAAT and 1.1% for ASAT, the inter‐observer coefficient of variation was 1.4% for IAAT and 1.2% for ASAT, the intra‐observer correlation was 0.998 for IAAT and 0.999 for ASAT, and the inter‐observer correlation was 0.999 for both IAAT and ASAT. These results indicate that precise and accurate measures of body fat content and distribution can be obtained in a fast and reliable form by the AMRA^TM Profiler, opening up the possibility of large‐scale human phenotypic studies. Copyright © 2015 John Wiley & Sons, Ltd.     

In vivo characterization of tissue thermal properties of the kidney during local hyperthermia induced by MR-guided high-intensity focused ultrasound

The purpose of this study was to evaluate quantitatively in vivo the tissue thermal properties during high-intensity focused ultrasound (HIFU) heating. For this purpose, a total of 52 localized sonications were performed in the kidneys of six pigs with HIFU monitored in real time by volumetric MR thermometry. The kidney perfusion was modified by modulation of the flow in the aorta by insertion of an inflatable angioplasty balloon. The resulting temperature data were analyzed using the bio-heat transfer model in order to validate the model under in vivo conditions and to estimate quantitatively the absorption (α), thermal diffusivity (D) and perfusion (w(b)) of renal tissue. An excellent correspondence was observed between the bio-heat transfer model and the experimental data. The absorption and thermal diffusivity were independent of the flow, with mean values (± standard deviation) of 20.7 ± 5.1 mm(3) K J(-1) and 0.23 ± 0.11 mm(2) s(-1), respectively, whereas the perfusion decreased significantly by 84% (p < 0.01) with arterial flow (mean values of w(b) of 0.06 ± 0.02 and 0.008 ± 0.007 mL(-1) mL s(-1)), as predicted by the model. The quantitative analysis of the volumetric temperature distribution during nondestructive HIFU sonication allows the determination of the thermal parameters, and may therefore improve the quality of the planning of noninvasive therapy with MR-guided HIFU.     

Functional and anatomical characterization of brown adipose tissue in heart failure with blood oxygen level dependent magnetic resonance

Recent studies have suggested that brown adipose tissue (BAT) plays an important role in obesity, insulin resistance and heart failure. The characterization of BAT in vivo, however, has been challenging. No technique to comprehensively image BAT anatomy and function has been described. Moreover, the impact on BAT of the neuroendocrine activation seen in heart failure has only recently begun to be evaluated in vivo. The aim of this study was to use MRI to characterize the impact of heart failure on the morphology and function of BAT. Mice subjected to permanent ligation of the left coronary artery were imaged with MRI 6 weeks later. T₂ weighted MRI of BAT volume and blood oxygen level dependent MRI of BAT function were performed. T₂* maps of BAT were obtained at multiple time points before and after administration of the β₃ adrenergic agonist CL 316 243 (CL). Blood flow to BAT was studied after CL injection using the flow alternating inversion recovery (FAIR) approach. Excised BAT tissue was analyzed for lipid droplet content and for uncoupling protein 1 (UCP1) mRNA expression. BAT volume was significantly lower in heart failure (51 ± 1 mm³ versus 65 ± 3 mm³; p < 0.05), and characterized by a reduction in lipid globules and a fourfold increase in UCP1 mRNA (p < 0.05). CL injection increased BAT T₂* in healthy animals but not in mice with heart failure (24 ± 4% versus 6 ± 2%; p < 0.01), consistent with an increase in flow in control BAT. This was confirmed by a significant difference in the FAIR response in BAT in control and heart failure mice. Heart failure results in the chronic activation of BAT, decreased BAT lipid stores and decreased BAT volume, and it is associated with a marked decrease in ability to respond to acute physiological stimuli. This may have important implications for substrate utilization and overall metabolic homeostasis in heart failure. Copyright © 2016 John Wiley & Sons, Ltd.     

At the crossroad of T cells, adipose tissue, and diabetes

The study of how different intracellular metabolic signaling pathways impact the control of self-immune tolerance and how metabolic dysregulation in overweight, obesity, and diabetes is able to alter self-immune tolerance are topics of intensive investigation. Recent evidence suggests that metabolic and autoimmune diseases, both characterized by chronic inflammation and an altered self-immune tolerance, are more common in affluent countries. The reasons for such phenomena are still not completely understood, but the 'metabolic pressure' induced by nutritional overload, typical of more developed countries, seems to play a role. In this context, the discovery of the adipose tissue-derived hormone leptin has shed fundamental insights on how these processes might occur. We believe that there is a strong relationship among leptin, metabolic state, and immunological self-tolerance. We hypothesize that the leptin-induced metabolic pressure sets the basis for an exaggerated immuno-inflammatory response to altered self or non-self, leading to chronic inflammation, metabolic dysregulation, and autoimmunity in subjects with risk factors (i.e. genetic predisposition, environment, sex, infectious agents, etc). Capitalizing on our joint effort and trans-disciplinary expertise in metabolism, self-tolerance, and autoimmune diseases, this review highlights key questions on the basic mechanisms governing immune tolerance in the context of metabolic and autoimmune disease susceptibility.     

白色脂肪"棕色化"调控因子FNDC5/Irisin的研究进展

肥胖是当下全球牵涉范围最广的慢性疾病,也是2型糖尿病、心脑血管疾病以及某些癌症的重要风险因素.其中"白色脂肪棕色化"是目前该领域研究的热点之一,即将体内的储存多余能量的白色脂肪组织(white adipose tissue,WAT)转变为促进消耗能量的棕色脂肪组织(brown adipose tissue,BAT).近年在肌细胞中发现的Ⅲ型纤连蛋白组件包含蛋白5(fibronectin typeⅢdomain containing 5,FNDC5)经胞外切除形成小分子多肽,名为Irisin,具有"白色脂肪棕色化"的功能.     

大鼠白色和棕色脂肪来源的间充质干细胞成脂分化特性的比较

目的探讨白色脂肪组织(WAT)和棕色脂肪组织(BAT)来源的间充质干细胞成脂分化特性的差异。方法雄性SD大鼠15只,3只用于细胞分离培养,12只用于细胞移植。体外分离培养WAT和BAT两种来源的脂肪干细胞,用油红O染色检测两种干细胞的成脂分化率,用免疫荧光技术检测成脂诱导、分化后的细胞是棕色脂肪细胞还是白色脂肪细胞。4’6-二脒基-2-苯基吲哚(DAPI)标记两种来源的干细胞后移植至腹股沟区,分别在第1、2、3周取材,免疫荧光技术检测植入细胞的分化趋向。结果 WAT来源的干细胞增殖速度明显快于BAT来源的干细胞,前者成脂分化率为0.205±0.069,后者为0.165±0.053,两种干细胞的成脂诱导率差异无统计学意义(P0.05)。两种干细胞分别植入体内后,在第1、2、3周发现,两种干细胞均表达棕色脂肪特异性蛋白解耦联蛋白1(UCP1)。结论 WAT和BAT来源的干细胞在体外及体内诱导成脂后均分化为棕色脂肪细胞。     

胆囊炎家兔体表循经高温现象对棕色脂肪组织UCP1mRNA表达的影响

目的观察实验性胆囊炎家兔体表循经高温现象产生对棕色脂肪组织中解偶联蛋白1(UCP1)mRNA表达的影响,探讨脂肪组织与循经高温现象的相关性。方法建立实验性胆囊炎家兔模型,并设空白对照组。红外温度计采集胆经部位温度后取材,Real-Time PCR检测胆经脂肪组织中UCP1基因在mRNA水平上的表达。结果胆经部位温度组间比较,模型组较空白对照组明显增高(P0.05);Real-Time PCR检测模型组脂肪组织中UCP1mRNA的表达量明显高于空白对照组(P0.05)。结论实验性胆囊炎家兔体表循经高温现象产生部位的棕色脂肪组织中UCP1mRNA表达水平增高。     

Quantitative image analysis in adipose tissue using an automated image analysis system: differential effects of peroxisome proliferator-activated receptor-alpha and -gamma agonist on white and brown adipose tissue morphology in AKR obese and db/db diabetic mice

Morphometric analysis of adipocytes is widely used to demonstrate the effects of antiobesity drugs or anti-diabetic drugs on adipose tissues. However, adipocyte morphometry has been quantitatively performed by manual object extraction using conventional image analysis systems. The authors have developed an automated quantitative image analysis method for adipose tissues using an innovative object-based quantitative image analysis system (eCognition). Using this system, it has been shown quantitatively that morphological features of adipose tissues of mice treated with peroxisome proliferator-activated receptor (PPAR) agonists differ dramatically depending on the type of PPAR agonist. Marked alteration of morphological characteristics of brown adipose tissue (BAT) treated with GI259578A, a PPAR-alpha agonist, was observed in AKR/J (AKR) obese mice. Furthermore, there was a 22.8% decrease in the mean size of adipocytes in white adipose tissue (WAT) compared with vehicle. In diabetic db/db mice, the PPAR-gamma agonist GW347845X decreased the mean size of adipocytes in WAT by 15.4% compared with vehicle. In contrast to changes in WAT, GW347845X increased the mean size of adipocytes in BAT greatly by 96.1% compared with vehicle. These findings suggest that GI259578A may activate fatty acid oxidation in BAT and that GW347845X may cause adipocyte differentiation in WAT and enhancement of lipid storage in BAT.     

Brown adipose tissue mapping in rats with combined intermolecular double‐quantum coherence and Dixon water–fat MRI

Brown adipose tissue (BAT) is a promising therapeutic target in obesity studies. Recently, MRI has been proposed for the mapping of BAT. However, because of the limitation of spatial resolution, similar to the existing positron emission tomography and computed tomography techniques for BAT detection, it fails to distinguish BAT cells when they are mixed with other cells. In this work, a new MRI method is proposed, combining intermolecular double‐quantum coherence and the chemical shift‐encoded Dixon method. Its contrast depends on the water to fat ratio at the cellular scale, which is smaller than the imaging voxel size. The feasibility of this MRI method was shown with computer simulations and phantoms, and preliminary imaging of BAT of rats at 7 T. Both computer simulations and experimental results are consistent with theoretical predictions. The method provides a novel contrast mechanism and can map BAT distribution exclusively. In particular, a mixture of BAT cells and white adipose tissue cells was detected in an older rat, which was undetectable by other noninvasive methods. This method may be applicable to a wide range of uses in BAT‐related studies, including the formation and variation of BAT. Copyright © 2013 John Wiley & Sons, Ltd.     

Endogenous lipid antigens for invariant natural killer T cells hold the reins in adipose tissue homeostasis

The global obesity epidemic and its associated co‐morbidities, including type 2 diabetes, cardiovascular disease and certain types of cancers, have drawn attention to the pivotal role of adipocytes in health and disease. Besides their ‘classical’ function in energy storage and release, adipocytes interact with adipose‐tissue‐resident immune cells, among which are lipid‐responsive invariant natural killer T (iNKT) cells. The iNKT cells are activated by lipid antigens presented by antigen‐presenting cells as CD1d/lipid complexes. Upon activation, iNKT cells can rapidly secrete soluble mediators that either promote or oppose inflammation. In lean adipose tissue, iNKT cells elicit a predominantly anti‐inflammatory immune response, whereas obesity is associated with declining iNKT cell numbers. Recent work showed that adipocytes act as non‐professional antigen‐presenting cells for lipid antigens. Here, we discuss endogenous lipid antigen processing and presentation by adipocytes, and speculate on how these lipid antigens, together with ‘environmental factors’ such as tissue/organ environment and co‐stimulatory signals, are able to influence the fate of adipose‐tissue‐resident iNKT cells, and thereby the role of these cells in obesity and its associated pathologies.     

Quantitative T2* imaging of metastatic human breast cancer to brain in the nude rat at 3 T

This study uses quantitative T₂* imaging to track ferumoxides–protamine sulfate (FEPro)‐labeled MDA‐MB‐231BR‐Luc (231BRL) human breast cancer cells that metastasize to the nude rat brain. Four cohorts of nude rats were injected intracardially with FEPro‐labeled, unlabeled or tumor necrosis factor‐related apoptosis‐inducing ligand(TRAIL)‐treated (to induce apoptosis) 231BRL cells, or saline, in order to develop metastatic breast cancer in the brain. The heads of the rats were imaged serially over 3–4 weeks using gradient multi‐echo and turbo spin‐echo pulse sequences at 3 T with a solenoid receive‐only 4‐cm‐diameter coil. Quantitative T₂* maps of the whole brain were obtained by the application of single‐exponential fitting to the signal intensity of T₂* images, and the distribution of T₂* values in brain voxels was calculated. MRI findings were correlated with Prussian blue staining and immunohistochemical staining for iron in breast cancer and macrophages. Quantitative analysis of T₂* from brain voxels demonstrated a significant shift to lower values following the intracardiac injection of FEPro‐labeled 231BRL cells, relative to animals receiving unlabeled cells, apoptotic cells or saline. Quartile analysis based on the T₂* distribution obtained from brain voxels demonstrated significant differences (p < 0.0083) in the number of voxels with T₂* values in the ranges 10–35 ms (Q1), 36–60 ms (Q2) and 61–86 ms (Q3) from 1 day to 3 weeks post‐infusion of labeled 231BRL cells, compared with baseline scans. There were no significant differences in the distribution of T₂* obtained from serial MRI in rats receiving unlabeled or TRAIL‐treated cells or saline. Histologic analysis demonstrated isolated Prussian blue‐positive breast cancer cells scattered in the brains of rats receiving labeled cells, relative to animals receiving unlabeled or apoptotic cells. Quantitative T₂* analysis of FEPro‐labeled metastasized cancer cells was possible even after the hypointense voxels were no longer visible on T₂*‐weighted images. Published in 2010 by John Wiley & Sons, Ltd.