The role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates

Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) may be effective in treating depression. Parental verbal abuse has been linked to decreased fractional anisotropy (FA) of white matter and reduced FA correlated with depression and anxiety scores. Utilizing a nonhuman primate model of mood and anxiety disorders following disrupted mother–infant attachment, we examined whether adverse rearing conditions lead to white matter impairment of the ALIC. We examined white matter integrity using Diffusion Tensor Imaging (DTI) on a 3T-MRI. Twenty-one adult male Bonnet macaques participated in this study: 12 were reared under adverse [variable foraging demand (VFD)] conditions whereas 9 were reared under normative conditions. We examined ALIC, posterior limb of the internal capsule (PLIC) and occipital white matter. VFD rearing was associated with significant reductions in FA in the ALIC with no changes evident in the PLIC or occipital cortex white matter. Adverse rearing in monkeys persistently impaired frontal white matter tract integrity, a novel substrate for understanding affective susceptibility.     

Can we differentiate true white matter fibers from pseudofibers inside a brain abscess cavity using geometrical diffusion tensor imaging metrics?

High fractional anisotropy (FA) usually reflects the orientation and integrity of white matter (WM) fibers. Other regions of increased FA have been described, such as brain abscesses, developing cortex, and areas of hemorrhage. It may not be possible to differentiate true fibers from the pseudofibers found inside an abscess cavity on the basis of FA and mean diffusivity (MD). The aim of this study was to differentiate true WM fibers from pseudo WM tracts inside the abscess cavity using geometrical diffusion tensor imaging metrics [linear anisotropy (CL), planar anisotropy (CP), and spherical anisotropy (CS)]. Diffusion tensor imaging was performed in 42 patients with brain abscess and 10 age/sex-matched controls. Automated segmentation using Java-based software divided the abscess cavity into two sub-regions with FA < 0.20 and FA > or = 0.20. Quantitation was carried out on the sub-regions of the abscess cavity with FA > or = 0.20. In healthy controls, regions of interest were placed on the corpus callosum, posterior limb of the internal capsule, and periventricular and subcortical WM. Significantly increased CP values were observed inside the abscess cavity compared with various normal WM regions. Significantly increased FA and CL values were observed in the abscess cavity compared with subcortical WM only. However decreased FA and CL values were observed in the cavity compared with the corpus callosum, posterior limb of the internal capsule, and periventricular WM. The 95% confidence intervals of means for the abscess cavity were well separated from those for WM in the case of CL and CP; however, they overlapped in the case of FA, MD, and CS. High CP with low CL inside the abscess cavity suggests that the shape of the diffusion tensor is predominantly planar, whereas it is linear in WM tracts. These geometrical indices may have advantages over FA for differentiating true from pseudo WM tracts inside the abscess cavity.     

Altered immune function of monocytes in different stages of patients with acute on chronic liver failure

The aim of this study was to investigate the characteristics of the immune function of monocytes in different stages of the patients with acute on chronic liver failure (ACLF). Human leucocyte antigen (HLA)-DR and Toll-like receptor 4 (TLR-4) expression on monocytes in early and late stages of acute on chronic liver failure were detected by flow cytometry. The secretion function of monocytes was measured by cytometric bead array. Compared with healthy controls, the levels of HLA-DR expression on monocytes in patients with chronic hepatitis B, liver cirrhosis and acute on chronic liver failure were gradually decreased, especially in the late stage of acute on chronic liver failure (P < 0.001). TLR-4 expression on monocytes in patients with liver cirrhosis and acute on chronic liver failure were higher than the healthy controls. The concentrations of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha and IL-12p70 in early-stage ACLF were significantly higher compared with healthy controls and lower in late-stage ACLF (P < 0.01, 0.05). However, a significantly lower amount of IL-10 was found on monocytes in early-stage ACLF than that of late-stage ACLF and healthy controls (P < 0.01). Monocyte HLA-DR expression in patients who died was significantly lower compared with patients who survived in the early and late stages of ACLF (P < 0.01). The dynamic detection of HLA-DR expression or cytokines secreted from monocytes could contribute to the estimation of the status of the immune function of patients with acute on chronic liver failure.     

首发重症抑郁症的弥散张量成像研究:基于纤维束示踪的空间统计学分析结果

目的:应用基于纤维束示踪的空间统计分析(Tract-Based Spatial Statistics,TBSS)方法,探讨重症抑郁症病患者全脑白质纤维的完整性是否受到损害。方法:对20(8男,12女)例重症抑郁症病患者组和20(8男,12女)例与抑郁症组按性别、年龄、教育程度匹配的正常人进行全脑弥散张量成像扫描。应用TBSS方法来比较两组的各向异性分数。结果:抑郁症组的左侧内囊前肢、右侧海马旁回、左侧后扣带回的各向异性分数显著低于正常组(P<0.05,t>3,校正),患者组内囊前肢的各向异性分数和抑郁症严重程度呈现负相关。结论:白质病变在抑郁症发病早期即已存在,这些病变区域主要涉及前额叶和边缘系统等与认知和情感调节关系较密切的神经环路的纤维束,这些改变可能导致皮层和皮层下连接受损,从而有利于深入了解抑郁症疾病的发病机理。     

Diffusion tensor MRI in rat models of invasive and well-demarcated brain tumors

Diffusion tensor imaging (DTI) and its metrics, such as mean diffusivity (MD) and fractional anisotropy (FA), have been used to detect the extent of brain tumors and understand tumor growth and its influence on the surrounding tissue. However, there are conflicting reports on how DTI metrics can be used for tumor diagnosis. The physiological interpretation of these metrics in terms of tumor growth is also not clear. The objective of this study was to investigate the DTI parameters in two rat brain tumor models (9L and F98) with different patterns of aggressiveness by longitudinal monitoring of tumor growth and comparing the DTI parameters of these two tumor models. In addition to the standard DTI metrics, MD and FA, we measured other metrics representing diffusion tensor shape, such as linear and planar anisotropy coefficients (CL and CP), and orientational coherence measured by lattice index (LI), to characterize the two tumor models. The 9L tumor had higher FA, CL, and LI than the F98 tumor. F98 had a larger difference in anisotropies between tumor and peritumor regions than 9L. From the eigenvalues, it was found that the increase in CL and trace of the 9L tumor was due to an increase in the primary eigenvalue, whereas the increase in CP in the peritumor region was due to an increase in both primary and secondary eigenvalues and a decrease in tertiary eigenvalue. Our results indicate that shape-oriented anisotropy measures, such as CL and CP, and orientational coherence measures, such as LI, can provide useful information in differentiating these two tumor models and also differentiating tumor from peritumoral regions.     

A complementary diffusion tensor imaging (DTI)-histological study in a model of Huntington's disease

In vivo diffusion tensor imaging (DTI) was performed on the quinolinic acid (QUIN) rat model of Huntington's disease, together with behavioral assessment of motor deficits and histopathological characterization. DTI and histology revealed the presence of a cortical lesion in 53% of the QUIN animals (QUIN^+ctx). Histologically, QUIN^+ctx were distinguished from QUIN^−ctx animals by increased astroglial reaction within a subregion of the caudate putamen and loss of white matter in the external capsula. Although both techniques are complementary, the quantitative character of DTI makes it possible to pick up subtle differences in tissue microstructure that are not identified with histology. DTI demonstrated differential changes of fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in the internal and external capsula, and within a subregion of the caudate putamen. It was suggested that FA increased due to a selective loss of the subcortical connections targeted by degenerative processes at the early stage of the disease, which might turn the striatum into a seemingly more organized structure. When tissue degeneration becomes more severe, FA decreased while AD, RD and MD increased.     

T1846 and A/G1913 are associated with acute on chronic liver failure in patients infected with hepatitis B virus genotypes B and C

The aim of this study was to determine whether mutations in the hepatitis B virus (HBV) genome are associated with the onset of acute on chronic liver failure (ACLF). For the longitudinal study, full‐length HBV genomes were cloned and sequenced from four ACLF patients and compared with sequences from matching samples collected before ACLF. For the cross‐sectional study, 166 serum samples were obtained, including 49 samples from patients with ACLF. The results of longitudinal study showed that C53T, A1846T, and G1896A were the most common mutations in association with ACLF. In the cross‐sectional study 61.2% patients with ACLF presented with T1846, which was higher than patients with chronic hepatitis B (CHB) (11.1%), liver cirrhosis (LC) (31.1%), and hepatocellular carcinoma (HCC) (33.3%). Prevalence of A/G1913 was 42.9% in patients with ACLF, also higher than patients with CHB (2.2%), LC (17.8%), and HCC (11.1%). There were no differences in HBV genotype and patients' HBeAg status among patients with ACLF, LC, and HCC. However, prevalence of T1846 was much higher in patients infected with genotype B (57.1%) than genotype C (30.4%). A/G1913 was higher in HBeAg negative patients (28%) than HBeAg positive patients (13.2%). Results of a multivariable analysis showed that T1846 and A/G1913 were independent factors for ACLF (OR = 3.373 and 4.244, respectively). Interestingly, T1846 destroys an ATG codon of a small open reading frame in the preC region, which may increase core protein expression. We conclude that T1846 and A/G1913 in the preC/C gene are closely associated with ACLF. J. Med. Virol. 83:996–1004, 2011. © 2011 Wiley‐Liss, Inc.     

Acute-on-chronic liver failure: recent update

Acute on chronic liver failure (ACLF) was first described in 1995 as a clinical syndrome distinct to classic acute decompensation. Characterized by complications of decompensation, ACLF occurs on a background of chronic liver dysfunction and is associated with high rates of organ failure and significant short-term mortality estimated between 45% and 90%. Despite the clinical relevance of the condition, it still remains largely undefined with continued disagreement regarding its precise etiological factors, clinical course, prognostic criteria and management pathways. It is concerning that, despite our relative lack of understanding of the condition, the burden of ACLF among cirrhotic patients remains significant with an estimated prevalence of 30.9%. This paper highlights our current understanding of ACLF, including its etiology, diagnostic and prognostic criteria and pathophysiology. It is evident that further refinement of the ACLF classification system is required in order to detect high-risk patients and improve short-term mortality rates. The field of metabolomics certainly warrants investigation to enhance diagnostic and prognostic parameters, while the use of granulocyte-colony stimulating factor is a promising future therapeutic intervention for patients with ACLF.     

HIV-associated alterations in normal-appearing white matter: a voxel-wise diffusion tensor imaging study

OBJECTIVE: There are conflicting reports of adverse HIV-associated alterations in white matter integrity as measured by diffusion tensor imaging (DTI). We sought to address these conflicting reports by assessing, on a voxel-by-voxel basis, HIV-associated regional changes in radiologically defined normal-appearing white matter (NAWM) integrity using high-resolution DTI. METHODS: 30 HIV-seropositive (SP) and 30 HIV-seronegative (SN) nondemented, community-dwelling participants underwent DTI to derive whole-brain measures of white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]). For each participant, the white matter T2 volume was thresholded to remove regions of abnormal signal, resulting in a NAWM mask, which was then applied to the FA and MD volumes to extract voxel-wise NAWM measures of white matter integrity. Voxel-wise group comparisons of FA and MD were conducted (P < 0.005, extent threshold 5 voxels) while controlling for age and substance-abuse history. RESULTS: There were no significant differences between the groups for demographic or cognitive performance variables. Summary whole-brain measures of FA and MD were equivalent between the SP and SN samples. Among the SP sample, history of substance abuse was associated with significantly increased whole-brain NAWM MD, and coinfection with hepatitis C virus (HCV) was associated with a trend for increased MD. Correlations between whole-brain NAWM FA and MD with cognitive performance measures were not significant. Regional analyses of DTI measures revealed variable differences in NAWM FA in the SP sample, with findings of both decreased and increased FA. Differences in NAWM MD were more consistent, with widespread increases noted in the SP sample compared to the SN sample. Eight of the 10 regions displaying significantly increased FA in the SP sample were also found to have significantly increased MD compared to the SN sample. CONCLUSIONS: Decreased white matter integrity is present even in radiologically defined NAWM in nondemented, community-dwelling patients with HIV. The decrease in NAWM integrity is best seen in increases in MD, a measure of generalized tissue breakdown. Indications of NAWM axonal integrity (FA) present a more complicated picture, with both decreased FA and increased FA in the SP sample. Our findings of variable HIV-associated FA changes in NAWM may account for previous conflicting reports of changes in DTI parameters in this population. The results of our study suggest that HIV infection contributes to variable changes in DTI values, reflecting both direct loss of axonal integrity and a loss of complexity to the underlying axonal matrix.     

Abnormal integrity of corticocortical tracts in mild cognitive impairment: a diffusion tensor imaging study

Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders.     

Age-related alterations in white matter microstructure measured by diffusion tensor imaging

Cerebral white matter (WM) undergoes various degenerative changes with normal aging, including decreases in myelin density and alterations in myelin structure. We acquired whole-head, high-resolution diffusion tensor images (DTI) in 38 participants across the adult age span. Maps of fractional anisotropy (FA), a measure of WM microstructure, were calculated for each participant to determine whether particular fiber systems of the brain are preferentially vulnerable to WM degeneration. Regional FA measures were estimated from nine regions of interest in each hemisphere and from the genu and splenium of the corpus callosum (CC). The results showed significant age-related decline in FA in frontal WM, the posterior limb of the internal capsule (PLIC), and the genu of the CC. In contrast, temporal and posterior WM was relatively preserved. These findings suggest that WM alterations are variable throughout the brain and that particular fiber populations within prefrontal region and PLIC are most vulnerable to age-related degeneration.     

Acute-on-chronic liver failure

Acute-on-chronic liver failure (ACLF) is an increasingly recognized distinct disease entity encompassing an acute deterioration of liver function in patients with chronic liver disease. Although there are no widely accepted diagnostic criteria for ACLF, the Asia.Pacific Association for the Study of the Liver (APASL) and the American Association for the Study of Liver Disease and the European Association for the Study of the Liver (AASLD/EASL) consensus definitions are commonly used. It is obvious that the APASL and the AASLD/EASL definitions are based on fundamentally different features. Two different definitions in two different parts of the world hamper the comparability of studies. Recently, the EASL-Chronic Liver Failure Consortium proposed new diagnostic criteria for ACLF based on analyses of patients with organ failure. There are areas of uncertainty in defining ACLF, such as heterogeneity of ACLF, ambiguity in qualifying underlying liver disease, argument for infection or sepsis as a precipitating event, etc. Although the exact pathogenesis of ACLF remains to be elucidated, alteration of host response to injury, infection, and unregulated inflammation play important roles. The predisposition, infection/inflammation, response, organ failure (PIRO) concept used for sepsis might be useful in describing the pathophysiology and clinical categories for ACLF. Treatment strategies are limited to organ support but better understanding of the pathophysiology is likely to lead to discovery of novel biomarkers and therapeutic strategies in the future.     

Diffusion tensor imaging of two unrelated Chinese men with hereditary spastic paraplegia associated with thin corpus callosum

Hereditary spastic paraplegia (HSP) associated with thin corpus callosum is a rare autosomal recessive neurodegenerative disorder characterized by an abnormally thin corpus callosum, normal motor development, slowly progressive spastic paraparesis and cognitive deterioration. To investigate and localize abnormalities in the brains of two Chinese patients with HSP-TCC, with mutations in the spatacsin gene. Diffusion tensor imaging (DTI) was used to determine the mean diffusion (MD) and fractional anisotropy (FA) in the brains of the patients in comparison to 20 healthy subjects. Voxel-based analysis (VBA) of both the diffusion and anisotropy values were performed using statistical parametric mapping (SPM). Significant changes with MD increase and FA reduction were found in the already known lesions including the corpus callosum, cerebellum and thalamus. In addition, changes were also found in regions that appear to be normal in conventional MRI, such as the brain stem, internal capsule, cingulum and subcortical white matter including superior longitudinal fascicle and inferior longitudinal fascicle. Neither increase in FA nor reduction in MD was detected in the brain. Our study provides clear in vivo MR imaging evidence of a more widespread brain involvement of HSP-TCC. MD is more sensitive than FA in detecting lesions in thalamus and subcortical white matter, suggesting that MD may be a better marker of the disease progression.     

The characteristic expression of B7‐H3 and B7‐H4 in liver biopsies from patients with HBV‐related acute‐on‐chronic liver failure

Hepatitis B virus (HBV) is a major public health problem, and HBV‐related acute‐on‐chronic liver failure (HBV‐ACLF) has an extremely poor prognosis due to a lack of effective treatments. B7‐H3 and B7‐H4 are two novel members of the B7 superfamily that are actively involved in regulating the pathogenesis of infectious diseases. However, the intrahepatic expression of both members in HBV‐ACLF patients has yet to be described. In this study, we analyzed the expression of B7‐H3 and B7‐H4 in HBV‐ACLF biopsies by immunohistochemistry. Our results showed that both members were observed in all HBV‐ACLF samples, and their expression was chiefly observed on infiltrating inflammatory cells and the damaged bile ducts. Immunofluorescence double staining showed that B7‐H4 was expressed chiefly on CD3⁺ T cells, CD68⁺ macrophages, CK‐18⁺ bile ducts, and CD31⁺ endothelial cells, while B7‐H3 was found on all cell types detected. The expression of the programmed death (PD)‐1 ligands, PD‐L1 and PD‐L2, was also detected in these liver tissues and they were found to be co‐expressed with B7‐H3 and B7‐H4. These results suggest that the B7‐family signaling is most likely to affect the pathogenesis of this disease, and a clear understanding of their functional roles may further elucidate the disease process.     

Diffusion tensor imaging demonstrates focal lesions of the corticospinal tract in hemiparetic patients with cerebral palsy

The purpose of this study was to use diffusion tensor imaging (DTI) with fiber tractography (FT) to demonstrate focal lesions of the corticospinal tract (CST) in hemiparetic patients with cerebral palsy (CP) who showed no specific focal lesions on conventional brain MRI. Four hemiparetic patients with CP (three left hemiparesis, mean age: 2.5 years, range: 0.9–7.0) and four age-matched controls were recruited. DTI was performed using a 1.5-T system with a synergy-L Sensitivity Encoding head coil. Fractional anisotropy (FA) and apparent diffusion coefficients (ADC) were measured using the region of interest (ROI) method. We estimated the asymmetric anisotropy index (AA) and asymmetric mean diffusivity index (AD) to evaluate the asymmetry between right and left CSTs. All four patients showed interrupted FT at the affected periventricular white matter (PVWM) level compared to that of the opposite side; this was not detected on conventional brain MRI and explained the hemiparesis of these patients. Compared to the data of controls, all patients showed significant AA and AD only at the PVWM level. DTI with FT demonstrated focal lesions at the PVWM level. We conclude that DTI with FT may be a useful modality for investigating focal lesions in hemiparetic patients with CP.     

脑深部核团MR弥散张量成像对帕金森病不同运动亚型的鉴别诊断价值

目的:探讨脑深部核团MR弥散张量成像(DTI)在帕金森病(PD)不同运动亚型中的鉴别诊断价值。方法:回顾性研究。纳入2017年10月—2019年12月南京大学医学院附属鼓楼医院47例PD患者的临床及MRI资料。按照统一PD评定量表第三部分(UPDRS Ⅲ)运动功能评分,将47例PD患者分为震颤为主型(TD)组30例和非...     

Aging in the CNS: comparison of gray/white matter volume and diffusion tensor data

This study investigated the global and regional effects of aging on brain volume, mean diffusivity (MD), and fractional anisotropy (FA) in 73 normal female subjects using voxel-based analysis. On a global scale, gray matter volume and FA were negatively correlated, whereas MD was positively correlated with age. Voxel-wise analyses showed brain volume and FA were negatively correlated predominantly in anterior structures, whereas MD was positively correlated in the cortical gray matter and periventricular white matter. Volume preservation was observed in the cingulate gyrus and subjacent white matter. FA increase was observed in the putamen. Voxel-based direct comparisons of volume and diffusion properties showed FA was more strongly negatively correlated in the fronto-temporal white matter, compared with volume and MD. Stronger positive correlation of MD was observed in the thalamus, caudate nucleus, and midbrain and stronger negative correlation of brain volume was observed in the frontal lobe and basal ganglia, compared with the other. These results indicate that diffusion properties and brain volume are complementary markers to the effects of aging.     

Brain diffusion tensor MRI in systematic lupus erythematosus: A systematic review

Diffusion tensor imaging (DTI) maps the brain's microstructure by measuring fractional anisotropy (FA) and mean diffusivity (MD). This systematic review describes brain diffusion tensor Magnetic resonance imaging (MRI) studies in systemic lupus erythematosus (SLE).The literature was reviewed following the PRISMA guidelines and using the terms “lupus”, “systemic lupus erythematosus”, “SLE”, “diffusion tensor imaging”, “DTI”, “white matter” (WM), “microstructural damage”, “tractography”, and “fractional anisotropy”; the search included articles published in English from January 2007 to April 2017. The subjects included in the study were selected according to the ACR criteria and included 195 SLE patients with neuropsychiatric manifestation (NPSLE), 299 without neuropsychiatric manifestation (non-NPSLE), and 423 healthy controls (HC). Most studies identified significantly reduced FA and increased MD values in several WM regions of both NPSLE and non-NPSLE patients compared to HC. Subclinical microstructural changes were observed in either regional areas or the entire brain in both the non-NPSLE and NPSLE groups.     

White matter damage of patients with Alzheimer’s disease correlated with the decreased cognitive function

Increasing evidence demonstrates that there is marked damage and dysfunction in the white matter in Alzheimer’s disease (AD). The present study investigates the nature of white matter damage of patients with Alzheimer’s disease with diffusion tensor magnetic resonance imaging (DTI) and analyses the relationship between the white matter damage and the cognition function. DTI, as well as T1 fluid attenuated inversion recovery (FLAIR) and T2-FLAIR, was performed on probable patients of Alzheimer’s disease, and sex and age matched healthy volunteers to measure the fractional anisotropy (FA) and mean diffusivity (MD) in the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, and the white matter of frontal, temporal, parietal, and occipital lobes. FA was lower in the splenium of corpus callosum, as well as in the white matter of the frontal, temporal, and parietal lobes from patients with Alzheimer’s disease than in the corresponding region from healthy controls and was strongly positive correlated with MMSE scores, whereas FA appeared no different in the anterior and posterior limbs of internal capsule, occipital lobes white matter, and the genu of corpus callosum between the patients and healthy controls. MD was significantly higher in the splenium of corpus callosum and parietal lobes white matter from patients than in that those from healthy controls and was strongly negative correlated with MMSE scores, whereas MD in the anterior and posterior limbs of internal capsule, as well as in frontal, temporal, occipital lobes white matter and the genu of corpus callosum, was not different between the patients and healthy controls. The most prominent alteration of FA and MD was in the splenium of corpus callosum. Our results suggested that white matter of patients with Alzheimer’s disease was selectively impaired and the extent of damage had a strong correlation with the cognitive function, and that selective impairment reflected the cortico–cortical and cortico–subcortical disconnections in the pathomechanism of Alzheimer’s disease. The values of FA and MD in white matter, especially in the splenium of corpus callosum in AD patients, might be a more appropriate surrogate marker for monitoring the disease progression.     

Characterization of diffuse fibrosis in the failing human heart via diffusion tensor imaging and quantitative histological validation

Non‐invasive imaging techniques are highly desirable as an alternative to conventional biopsy for the characterization of the remodeling of tissues associated with disease progression, including end‐stage heart failure. Cardiac diffusion tensor imaging (DTI) has become an established method for the characterization of myocardial microstructure. However, the relationships between diffuse myocardial fibrosis, which is a key biomarker for staging and treatment planning of the failing heart, and measured DTI parameters have yet to be investigated systematically. In this study, DTI was performed on left ventricular specimens collected from patients with chronic end‐stage heart failure as a result of idiopathic dilated cardiomyopathy (n = 14) and from normal donors (n = 5). Scalar DTI parameters, including fractional anisotropy (FA) and mean (MD), primary (D₁), secondary (D₂) and tertiary (D₃) diffusivities, were correlated with collagen content measured by digital microscopy. Compared with hearts from normal subjects, the FA in failing hearts decreased by 22%, whereas the MD, D₂ and D₃ increased by 12%, 14% and 24%, respectively (P < 0.01). No significant change was detected for D₁ between the two groups. Furthermore, significant correlation was observed between the DTI scalar indices and quantitative histological measurements of collagen (i.e. fibrosis). Pearson's correlation coefficients (r) between collagen content and FA, MD, D₂ and D₃ were –0.51, 0.59, 0.56 and 0.62 (P < 0.05), respectively. The correlation between D₁ and collagen content was not significant (r = 0.46, P = 0.05). Computational modeling analysis indicated that the behaviors of the DTI parameters as a function of the degree of fibrosis were well explained by compartmental exchange between myocardial and collagenous tissues. Combined, these findings suggest that scalar DTI parameters can be used as metrics for the non‐invasive assessment of diffuse fibrosis in failing hearts. Copyright © 2014 John Wiley & Sons, Ltd.