Accuracy of fully automated,quantitative, volumetric measurement of the amount of fibroglandular breast tissue using MRI: correlation with anthropomorphic breast phantoms

To demonstrate the accuracy of fully automated, quantitative, volumetric measurement of the amount of fibroglandular breast tissue (FGT), using MRI, and to investigate the impact of different MRI sequences using anthropomorphic breast phantoms as the ground truth. In this study, 10 anthropomorphic breast phantoms that consisted of different known fractions of adipose and protein tissue, which closely resembled normal breast parenchyma, were developed. Anthropomorphic breast phantoms were imaged with a 1.5 T unit (Siemens, Avantofit) using an 18‐channel breast coil. The sequence protocol consisted of an isotropic Dixon sequence (Di), an anisotropic Dixon sequence (Da), and T₁ 3D FLASH sequences with and without fat saturation (T1). Fully automated, quantitative, volumetric measurement of FGT for all anthropomorphic phantoms and sequences was performed and correlated with the amounts of fatty and protein components in the phantoms as the ground truth. Fully automated, quantitative, volumetric measurements of FGT with MRI for all sequences ranged from 5.86 to 61.05% (mean 33.36%). The isotropic Dixon sequence yielded the highest accuracy (median 0.51%–0.78%) and precision (median range 0.19%) compared with anisotropic Dixon (median 1.92%–2.09%; median range 0.55%) and T₁‐weighted sequences (median 2.54%–2.46%; median range 0.82%). All sequences yielded good correlation with the FGT content of the anthropomorphic phantoms. The best correlation of FGT measurements was identified for Dixon sequences (Di, R² = 0.999; Da, R² = 0.998) compared with conventional T₁‐weighted sequences (R² = 0.971). MRI yields accurate, fully automated, quantitative, volumetric measurements of FGT, an increasingly important and sensitive imaging biomarker for breast cancer risk. Compared with conventional T₁ sequences, Dixon‐type sequences show the highest correlation and reproducibility for automated, quantitative, volumetric FGT measurements using anthropomorphic breast phantoms as the ground truth.     

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.     

Diffusion‐weighted imaging of normal fibroglandular breast tissue: influence of microperfusion and fat suppression technique on the apparent diffusion coefficient

The influence of microperfusion and fat suppression technique on the apparent diffusion coefficient (ADC) values obtained with diffusion weighted imaging (DWI) of normal fibroglandular breast tissue was investigated. Seven volunteers (14 breasts) were scanned using diffusion weighting factors (b values) up to 1600 s/mm² and the four different fat suppression techniques: STIR, fat saturation, SPAIR, and Water Excitation. The relationship between the logarithmic DW attenuation curves and b was linear for b values up to 600 s/mm² (R² > 0.999). Small differences were noted between the ADC values obtained with the various fat suppression methods, especially at the higher b values. Water Excitation had the highest mean SNR, exceeding STIR (p = 0.03) though not significantly different from fat saturation and SPAIR. In conclusion, the ADC of fibroglandular breast tissue is not influenced by microperfusion and Water Excitation is recommended because it yielded the best SNR values. These factors may be crucial in the differentiation between benign and malignant lesions. Copyright © 2010 John Wiley & Sons, Ltd.     

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.     

Quantification of the triglyceride fatty acid composition with 3.0 T MRI

The aim of this work was to validate a sequential method for quantifying the triglyceride fatty acid composition with 3.0 T MRI. The image acquisition was performed with a 3D spoiled gradient multiple echo sequence. A specific phase correction algorithm was implemented to correct the native phase images for wrap, zero‐ and first‐order phase and rebuild the real part images. Then, using a model of a fat ¹H MR spectrum integrating nine components, the number of double bonds (ndb) and the number of methylene‐interrupted double bonds (nmidb) were derived. The chain length (CL) was obtained from these parameters using heuristic approximation. Validations were performed on different vegetable oils whose theoretical fatty acid composition was used as reference and in five human subjects. In vivo measurements were made in the liver and in the subcutaneous and visceral adipose tissues. Linear regressions showed strong correlations between ndb and nmidb quantified with MRI and the theoretical values calculated using oil composition. Mean ndb/nmidb/CL were 1.80 ± 0.25/0.51 ± 0.21/17.43 ± 0.07, 2.72 ± 0.31/0.94 ± 0.16/17.47 ± 0.08 and 2.53 ± 0.21/0.84 ± 0.14/17.43 ± 0.07 in the liver, subcutaneous and visceral adipose tissues respectively. The results suggest that the triglyceride fatty acid composition can be assessed in human fatty liver and adipose tissues with a clinically relevant MRI method at 3.0 T. Copyright © 2014 John Wiley & Sons, Ltd.     

High‐resolution MRI analysis of breast cancer xenograft on the chick chorioallantoic membrane

The chick chorioallantoic membrane (CAM) model has been successfully used to study angiogenesis, cancer progression and its pharmacological treatment, tumor pharmacokinetics, and properties of novel nanomaterials. MRI is an attractive technique for non‐invasive and longitudinal monitoring of physiological processes and tumor growth. This study proposes an age‐adapted cooling regime for immobilization of the chick embryo, enabling high‐resolution MRI of the embryo and the CAM tumor xenograft. 64 chick embryos were enrolled in this study. The novel immobilization and imaging protocol was optimized in 29 embryos. From d7 to d18 immobilization of the embryo up to 90 min was achieved by cooling at 4 °C pre‐imaging, with cooling times adapted to age. Its application to tumor growth monitoring was evaluated in 15 embryos after xenotransplantation of human MDA‐MB‐231 breast cancer cells on CAM. Tumor volumes were monitored from d4 to d9 after grafting (d11 to d16 after incubation) applying a T₂‐weighted multislice RARE sequence. At d9 after grafting, the tumors were collected and compared with the MRI‐derived data by histology and weight measurements. Additional imaging methods comprising DWI, T₂ mapping, and the bio‐distribution of contrast agents were tested at d9 after grafting in 20 further embryos. With the adaptive cooling regime, motion artifacts could be completely avoided for up to 90 min scan time, enabling high‐resolution in ovo imaging. Excellent anatomical details could be obtained in the embryo and tumors. Tumor volumes could be quantified over time. The results prove the feasibility of high‐resolution MRI for longitudinal tumor and organ growth monitoring. The suggested method is promising for future applications such as testing tailored and/or targeted treatment strategies, longitudinal monitoring of tumor development, analysis of therapeutic efficacies of drugs, or assessment of tumor pharmacokinetics. The method provides an alternative to animal experimentation. Copyright © 2015 John Wiley & Sons, Ltd.     

Relationship between diffusion parameters derived from intravoxel incoherent motion MRI and perfusion measured by dynamic contrast‐enhanced MRI of soft tissue tumors

Our aim was to evaluate the link between diffusion parameters measured by intravoxel incoherent motion (IVIM) diffusion‐weighted imaging (DWI) and the perfusion metrics obtained with dynamic contrast‐enhanced (DCE) MRI in soft tissue tumors (STTs). Twenty‐eight patients affected by histopathologically confirmed STT were included in a prospective study. All patients underwent both DCE MRI and IVIM DWI. The perfusion fraction f, diffusion coefficient D and perfusion‐related diffusion coefficient D* were estimated using a bi‐exponential function to fit the DWI data. DCE MRI was acquired with a temporal resolution of 3–5 s. Maps of the initial area under the gadolinium concentration curve (IAUGC), time to peak (TTP) and maximum slope of increase (MSI) were derived using commercial software. The relationships between the DCE MRI and IVIM DWI measurements were assessed by Spearman's test. To exclude false positive results under multiple testing, the false discovery rate (FDR) procedure was applied. The Mann–Whitney test was used to evaluate the differences between all variables in patients with non‐myxoid and myxoid STT. No significant relationship was found between IVIM parameters and any DCE MRI parameters. Higher f and D*f values were found in non‐myxoid tumors compared with myxoid tumors (p = 0.004 and p = 0.003, respectively). MSI was significantly higher in non‐myxoid tumors than in myxoid tumors (p = 0.029). From the visual assessments of single clinical cases, both f and D*f maps were in satisfactory agreement with DCE maps in the extreme cases of an avascular mass and a highly vascularized mass, whereas, for tumors with slight vascularity or with a highly heterogeneous perfusion pattern, this association was not straightforward. Although IVIM DWI was demonstrated to be feasible in STT, our data did not support evident relationships between perfusion‐related IVIM parameters and perfusion measured by DCE MRI. Copyright © 2015 John Wiley & Sons, Ltd.     

Multi‐parametric MRI characterization of healthy human thigh muscles at 3.0 T – relaxation,magnetization transfer,fat/water,and diffusion tensor imaging

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo‐pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin‐echo T₂ imaging (with and without fat signal suppression, FS), selective inversion recovery for T₁ and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re‐imaged an average of 35 days later. Pre‐testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between‐day intra‐class correlations were observed in all quantitative indices except for the macromolecular‐to‐free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two‐way analysis of variance revealed no significant between‐day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland–Altman plots, and low repeatability coefficients were obtained for all parameters. Among‐muscle differences in the quantitative MRI indices and inter‐class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T₁, T₂, fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters. Copyright © 2014 John Wiley & Sons, Ltd.     

Reliability and agreement of adipose tissue fat fraction measurements with water–fat MRI in patients with manifest cardiovascular disease

The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical‐shift water–fat multi‐echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficient_agreement, ICC_agreement) was 0.97 for test–retest, 0.95 for intra‐observer and 0.56 for inter‐observer measurements, which increased to 0.88 when ICC_consistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) ?1.7 to 2.6) for test–retest, ?0.5% (LoA ?2.9 to 2.0) for intra‐observer and 5.6% (LoA 0.4 to 10.8) for inter‐observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6–84.0) and 89.7% (IQR 87.2–91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water–fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantitative susceptibility mapping of the spine using in‐phase echoes to initialize inhomogeneous field and R2* for the nonconvex optimization problem of fat‐water separation

Quantitative susceptibility mapping (QSM) of human spinal vertebrae from a multi‐echo gradient‐echo (GRE) sequence is challenging, because comparable amounts of fat and water in the vertebrae make it difficult to solve the nonconvex optimization problem of fat‐water separation (R2*‐IDEAL) for estimating the magnetic field induced by tissue susceptibility. We present an in‐phase (IP) echo initialization of R2*‐IDEAL for QSM in the spinal vertebrae. Ten healthy human subjects were recruited for spine MRI. A 3D multi‐echo GRE sequence was implemented to acquire out‐phase and IP echoes. For the IP method, the R2* and field maps estimated by separately fitting the magnitude and phase of IP echoes were used to initialize gradient search R2*‐IDEAL to obtain final R2*, field, water, and fat maps, and the final field map was used to generate QSM. The IP method was compared with the existing Zero method (initializing the field to zero), VARPRO‐GC (variable projection using graphcuts but still initializing the field to zero), and SPURS (simultaneous phase unwrapping and removal of chemical shift using graphcuts for initialization) on both simulation and in vivo data. The single peak fat model was also compared with the multi‐peak fat model. There was no substantial difference on QSM between the single peak and multi‐peak fat models, but there were marked differences among different initialization methods. The simulations demonstrated that IP provided the lowest error in the field map. Compared to Zero, VARPRO‐GC and SPURS, the proposed IP method provided substantially improved spine QSM in all 10 subjects.     

Histogram analysis of quantitative T1 and MT maps from ultrahigh field MRI in clinically isolated syndrome and relapsing–remitting multiple sclerosis

This study used quantitative MRI to study normal appearing white matter (NAWM) in patients with clinically isolated syndromes suggestive of multiple sclerosis and relapsing–remitting multiple sclerosis (RRMS). This was done at ultrahigh field (7 T) for greater spatial resolution and sensitivity. 17 CIS patients, 11 RRMS patients, and 20 age‐matched healthy controls were recruited. They were scanned using a 3D inversion recovery turbo field echo sequence to measure the longitudinal relaxation time (T₁). A 3D magnetization transfer prepared turbo field echo (MT‐TFE) sequence was also acquired, first without a presaturation pulse and then with the MT presaturation pulse applied at ?1.05 kHz and +1.05 kHz off resonance from water to produce two magnetization transfer ratio maps (MTR(?) and MTR(+)). Histogram analysis was performed on the signal from the voxels in the NAWM mask. The upper quartile cut‐off of the T₁ histogram was significantly higher in RRMS patients than in controls (p < 0.05), but there was no difference in CIS. In contrast, MTR was significantly different between CIS or RRMS patients and controls (p < 0.05) for most histogram measures considered. The difference between MTR(+) and MTR(?) signals showed that NOE contributions dominated the changes found. There was a weak negative correlation (r = ?0.46, p < 0.05) between the mode of T₁ distributions and healthy controls' age; this was not significant for MTR(+) (r = ?0.34, p > 0.05) or MTR(?) (r = 0.13, p > 0.05). There was no significant correlation between the median of T₁, MTR(?), or MTR(+) and the age of healthy controls. Furthermore, no significant correlation was observed between EDSS or disease duration and T₁, MTR(?), or MTR(+) for either CIS or RRMS patients. In conclusion, MTR was found to be more sensitive to early changes in MS disease than T₁. Copyright © 2015 John Wiley & Sons, Ltd.