A chemical signal in human female tears lowers aggression in males.

Rodent tears contain social chemosignals with diverse effects, including blocking male aggression. Human tears also contain a chemosignal that lowers male testosterone, but its behavioral significance was unclear. Because reduced testosterone is associated with reduced aggression, we tested the hypothesis that human tears act like rodent tears to block male aggression. Using a standard behavioral paradigm, we found that sniffing emotional tears with no odor percept reduced human male aggression by 43.7%. To probe the peripheral brain substrates of this effect, we applied tears to 62 human olfactory receptors in vitro. We identified 4 receptors that responded in a dose-dependent manner to this stimulus. Finally, to probe the central brain substrates of this effect, we repeated the experiment concurrent with functional brain imaging. We found that sniffing tears increased functional connectivity between the neural substrates of olfaction and aggression, reducing overall levels of neural activity in the latter. Taken together, our results imply that like in rodents, a human tear-bound chemosignal lowers male aggression, a mechanism that likely relies on the structural and functional overlap in the brain substrates of olfaction and aggression. We suggest that tears are a mammalian-wide mechanism that provides a chemical blanket protecting against aggression.

Increased cortical inhibition following brief motor memory reactivation supports reconsolidation and overnight offline learning gains.

Practicing motor skills stabilizes and strengthens motor memories by repeatedly reactivating and reconsolidating them. The conventional view, by which a repetitive practice is required for substantially improving skill performance, has been recently challenged by behavioral experiments, in which even brief reactivations of the motor memory have led to significant improvements in skill performance. However, the mechanisms which facilitate brief reactivation-induced skill improvements remain elusive. While initial memory consolidation has been repeatedly associated with increased neural excitation and disinhibition, reconsolidation has been shown to involve a poorly understood mixture of both excitatory and inhibitory alterations. Here, we followed a 3-d reactivation-reconsolidation framework to examine whether the excitatory/inhibitory mechanisms which underlie brief reactivation and repetitive practice differ. Healthy volunteers practiced a motor sequence learning task using either brief reactivation or repetitive practice and were assessed using ultrahigh field (7T) magnetic resonance spectroscopy at the primary motor cortex (M1). We found that increased inhibition (GABA concentrations) and decreased excitation/inhibition (glutamate/GABA ratios) immediately following the brief reactivation were associated with overnight offline performance gains. These gains were on par with those exhibited following repetitive practice, where no correlations with inhibitory or excitatory changes were observed. Our findings suggest that brief reactivation and repetitive practice depend on fundamentally different neural mechanisms and that early inhibition-and not excitation-is particularly important in supporting the learning gains exhibited by brief reactivation.

Reducing blood flow pulsation artifacts in 3D time-of-flight angiography by locally scrambling the order of the acquisition at 3 T and 7 T.

PURPOSE: Non-contrast-enhanced time of flight (TOF) is a standard method for magnetic resonance angiography used to depict vessel morphology. TOF is commonly performed with a 3D steady-state acquisition, employing a short repetition time to support high resolution imaging. At 7 T, TOF exhibits substantial increase in SNR and contrast, improving its clinical value. However, one of the remaining challenges, exacerbated at 7 T, is the presence of artifacts due to pulsatile blood flow, especially near major blood vessels. In this study we examine a method to significantly reduce these artifacts. METHODS: We recently introduced a new "local-scrambling" approach that semi-randomizes the acquisition order of the phase encodes, to achieve a controllable cutoff frequency above which the artifacts are drastically reduced. With this approach, artifacts resulting from fast local fluctuations such as cardiac pulsation are significantly reduced. In this study, we explore the ability of this local-scrambling approach to reduce pulsatile blood flow artifacts in a 3D TOF acquisition. Cartesian line-by-line and center-out ordering, with and without local-scrambling, were compared in simulations and in human brain imaging at 3 and 7 T scanners. RESULTS: In the simulations the artifact intensity showed a 10-fold reduction using local-scrambling compared to line-by-line and 4-fold compared to center-out ordering. In vivo results show that artifacts are much more pronounced at 7 T compared to 3 T, and in both cases they are effectively reduced by local-scrambling. CONCLUSION: Local-scrambling improves image quality for both line-by-line and center-out ordering. This approach can easily be implemented in the scanner without any changes to the reconstruction.

Probing lipids relaxation times in breast cancer using magnetic resonance spectroscopic fingerprinting.

OBJECTIVES: To investigate the clinical relevance of the relaxation times of lipids within breast cancer and normal fibroglandular tissue in vivo, using magnetic resonance spectroscopic fingerprinting (MRSF). METHODS: Twelve patients with biopsy-confirmed breast cancer and 14 healthy controls were prospectively scanned at 3 T using a protocol consisting of diffusion tensor imaging (DTI), MRSF, and dynamic contrast-enhanced (DCE) MRI. Single-voxel MRSF data was recorded from the tumor (patients) - identified using DTI - or normal fibroglandular tissue (controls), in under 20 s. MRSF data was analyzed using in-house software. Linear mixed model analysis was used to compare the relaxation times of lipids in breast cancer VOIs vs. normal fibroglandular tissue. RESULTS: Seven distinguished lipid metabolite peaks were identified and their relaxation times were recorded. Of them, several exhibited statistically significant changes between controls and patients, with strong significance (p < 10-3) recorded for several of the lipid resonances at 1.3 ppm (T1 = 355 ± 17 ms vs. 389 ± 27 ms), 4.1 ppm (T1 = 255 ± 86 ms vs. 127 ± 33 ms), 5.22 ppm (T1 = 724 ± 81 ms vs. 516 ± 62 ms), and 5.31 ppm (T2 = 56 ± 5 ms vs. 44 ± 3.5 ms, respectively). CONCLUSIONS: The application of MRSF to breast cancer imaging is feasible and achievable in clinically relevant scan time. Further studies are required to verify and comprehend the underling biological mechanism behind the differences in lipid relaxation times in cancer and normal fibroglandular tissue. KEY POINTS: •The relaxation times of lipids in breast tissue are potential markers for quantitative characterization of the normal fibroglandular tissue and cancer. •Lipid relaxation times can be acquired rapidly in a clinically relevant manner using a single-voxel technique, termed MRSF. •Relaxation times of T1 at 1.3 ppm, 4.1 ppm, and 5.22 ppm, as well as of T2 at 5.31 ppm, were significantly different between measurements within breast cancer and the normal fibroglandular tissue.

Quantifying the excitatory-inhibitory balance: A comparison of SemiLASER and MEGA-SemiLASER for simultaneously measuring GABA and glutamate at 7T.

The importance of the excitatory-inhibitory (E/I) balance in a wide range of cognitive and behavioral processes has prompted a commensurate interest in methods for reliably quantifying it. Proton Magnetic Resonance Spectroscopy (1H-MRS) remains the only method capable of safely and non-invasively measuring the concentrations of the brain's major excitatory (glutamate) and inhibitory (γ-aminobutyric-acid, GABA) neurotransmitters in-vivo. MRS relies on spectral Mescher-Garwood (MEGA) editing techniques at 3T to distinguish GABA from its overlapping resonances. However, with the increased spectral resolution at ultrahigh field strengths of 7T and above, non-edited spectroscopic techniques become potential viable alternatives to MEGA based approaches, and also address some of their shortcomings, such as signal loss, sensitivity to transmitter inhomogeneities and temporal resolution. We present a comprehensive comparison of both edited and non-edited strategies at 7T for simultaneously quantifying glutamate and GABA from the dorsal anterior cingulate cortex (dACC), and evaluate their reproducibility and relative bias. The combined root-mean-square test-retest reproducibility of Glu and GABA (CVE/I) was as low as 13.3% for unedited MRS at TE=80 ms using SemiLASER localization, while edited MRS at TE=80 ms yielded CVE/I=20% and 21% for asymmetric and symmetric MEGA editing, respectively. An unedited SemiLASER acquisition using a shorter echo time of TE=42 ms yielded CVE/I as low as 24.9%. Our results show that non-edited sequences at an echo time of 80 ms provide better reproducibility than either edited sequences at the same TE, or non-edited sequences at a shorter TE of 42 ms. This is supported by numerical simulations and is driven in part by a pseudo-singlet appearance of the GABA multiplets at TE=80 ms, and the excellent spectral resolution at 7T. Our results uphold a transition to non-edited MRS for monitoring the E/I balance at ultrahigh fields, and stress the importance of using a properly-optimized echo time.

Realistic head-shaped phantom with brain-mimicking metabolites for 7 T spectroscopy and spectroscopic imaging.

PURPOSE: Moving to ultra-high fields (≥7 T), the inhomogeneity of both RF (B1 ) and static (B0 ) magnetic fields increases, which further motivates us to design a realistic head-shaped phantom, especially for spectroscopic imaging. Such phantoms provide images similar to the human brain and serve as a reliable tool for developing and examining methods in MRI. This study aims to develop and characterize a realistic head-shaped phantom filled with brain-mimicking metabolites for MRS and magnetic resonance spectroscopic imaging in a 7 T MRI scanner. METHODS: A 3D head-shaped container with three sections-mimicking brain, muscle and precranial lipid-was constructed. The phantom was designed to provide robustness to heating, mechanical damage and leakage, with easy refilling. The head's shape and the agarose mixture were optimized to provide B0 and B1 distributions and T1 /T2 relaxation values similar to those of human brain. Eight brain-tissue-mimicking metabolites were included for spectroscopy. The phantom was evaluated for localized spectroscopy, fast spectroscopic imaging and fat suppression. RESULTS: The B0 and B1 maps showed distribution similar to that of human brain, with increased B0 inhomogeneity near the nasal and ear areas and reduced B1 in the temporal lobe and brain stem regions, as expected in vivo. The metabolites' concentrations were verified by single-voxel spectroscopy, showing an average deviation of 11%. Fast spectroscopic imaging and imaging with fat suppression were demonstrated. CONCLUSION: A 3D head-shaped phantom for human brain imaging and spectroscopic imaging in 7 T MRI was demonstrated, making it a realistic phantom for methodology development at 7 T.

Odor Canopy: A Method for Comfortable Odorant Delivery in MRI.

Functional magnetic resonance imaging (fMRI) has become the leading method for measuring the human brain response to sensory stimuli. However, olfaction fMRI lags behind vision and audition fMRI for 2 primary reasons: First, the olfactory brain areas are particularly susceptible to imaging artifacts, and second, the olfactory stimulus is particularly difficult to control in the fMRI environment. A component of the latter is related to the odorant delivery human-machine interface, namely the point where odorants exit the dispensing apparatus to reach at the nose. Previous approaches relied on either nasal cannulas or nasal masks, each associated with particular drawbacks and discomforts. Here, we provide detailed descriptions and instructions for transforming the MRI head-coil into an olfactory microenvironment, or odor canopy, where odorants can be switched on and off in less than 150 ms without cannula or mask. In a proof-of-concept experiment, we demonstrate that odor canopy provides for clearly dissociable odorant presence and absence, with no nonolfactory cues. Moreover, we find that odor canopy is rated more comfortable than nasal mask, and we demonstrate that using odor canopy in the fMRI generates a typical olfactory brain response. We conclude in recommending this approach for minimized discomfort in fMRI of olfaction.

Diffusivity in breast malignancies analyzed for b > 1000 s/mm2 at 1 mm in-plane resolutions: Insight from Gaussian and non-Gaussian behaviors.

Diffusion-weighted imaging (DWI) can improve breast cancer characterizations, but often suffers from low image quality -particularly at informative b > 1000 s/mm2 values. The aim of this study was to evaluate multishot approaches characterizing Gaussian and non-Gaussian diffusivities in breast cancer. This was a prospective study, in which 15 subjects, including 13 patients with biopsy-confirmed breast cancers, were enrolled. DWI was acquired at 3 T using echo planar imaging (EPI) with and without zoomed excitations, readout-segmented EPI (RESOLVE), and spatiotemporal encoding (SPEN); dynamic contrast-enhanced (DCE) data were collected using three-dimensional gradient-echo T1 weighting; anatomies were evaluated with T2 -weighted two-dimensional turbo spin-echo. Congruence between malignancies delineated by DCE was assessed against high-resolution DWI scans with b-values in the 0-1800 s/mm2 range, as well as against apparent diffusion coefficient (ADC) and kurtosis maps. Data were evaluated by independent magnetic resonance scientists with 3-20 years of experience, and radiologists with 6 and 20 years of experience in breast MRI. Malignancies were assessed from ADC and kurtosis maps, using paired t tests after confirming that these values had a Gaussian distribution. Agreements between DWI and DCE datasets were also evaluated using Sorensen-Dice similarity coefficients. Cancerous and normal tissues were clearly separable by ADCs: by SPEN their average values were (1.03 ± 0.17) × 10-3 and (1.69 ± 0.19) × 10-3  mm2 /s (p < 0.0001); by RESOLVE these values were (1.16 ± 0.16) × 10-3 and (1.52 ± 0.14) × 10-3 (p = 0.00026). Kurtosis also distinguished lesions (K = 0.64 ± 0.15) from normal tissues (K = 0.45 ± 0.05), but only when measured by SPEN (p = 0.0008). The best statistical agreement with DCE-highlighted regions arose for SPEN-based DWIs recorded with b = 1800 s/mm2 (Sorensen-Dice coefficient = 0.67); DWI data recorded with b = 850 and 1200 s/mm2 , led to lower coefficients. Both ADC and kurtosis maps highlighted the breast malignancies, with ADCs providing a more significant separation. The most promising alternative for contrast-free delineations of the cancerous lesions arose from b = 1800 s/mm2 DWI. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 3.

Inter-participant consistency of language-processing networks during abstract thoughts.

Human brain imaging typically employs structured and controlled tasks to avoid variable and inconsistent activation patterns. Here we expand this assumption by showing that an extremely open-ended, high-level cognitive task of thinking about an abstract content, loosely defined as "abstract thinking" - leads to highly consistent activation maps. Specifically, we show that activation maps generated during such cognitive process were precisely located relative to borders of well-known networks such as internal speech, visual and motor imagery. The activation patterns allowed decoding the thought condition at >95%. Surprisingly, the activated networks remained the same regardless of changes in thought content. Finally, we found remarkably consistent activation maps across individuals engaged in abstract thinking. This activation bordered, but strictly avoided visual and motor networks. On the other hand, it overlapped with left lateralized language networks. Activation of the default mode network (DMN) during abstract thought was similar to DMN activation during rest. These observations were supported by a quantitative neuronal distance metric analysis. Our results reveal that despite its high level, and varied content nature - abstract thinking activates surprisingly precise and consistent networks in participants' brains.

Diffusion-weighted breast MRI of malignancies with submillimeter resolution and immunity to artifacts by spatiotemporal encoding at 3T.

PURPOSE: Diffusion weighted imaging (DWI) is increasingly used in evaluating breast cancer, as complement to DCE measurements of superior spatial resolution. Extracting fine morphological features in DWI is complicated by limitations that sequences such as EPI face, when applied to heterogeneous organs. This study investigates the ability of spatiotemporal encoding (SPEN) MRI to screen breast cancers and define diffusivity features at mm and sub-mm resolutions on a 3T scanner METHODS: Twenty-one patients with biopsy-confirmed breast cancer lesions were examined by T2-weighted and DCE protocols, by EPI-based DWI, and by SPEN-based protocols optimized for SNR, robustness and spatial resolution, respectively. RESULTS: Excellent agreement was found between the diffusivity parameters measured by all SPEN protocols and by EPI, with the lower ADCs characteristic of tumors being readily detected. SPEN provided systematically better SNR and improved qualitative results, particularly when dealing with small lesions surrounded by fatty tissue, or lesions close to tissue/air interfaces. SPEN-derived ADC maps collected at sub-mm in-plane resolutions recapitulated the high-resolution morphology shown by lesions using more sensitive DCE protocols. CONCLUSION: Measurements on a patient cohort validated SPEN's ability to quantify the diffusivity changes associated with the presence of breast cancers, while imaging the lesions with reduced distortions at sub-mm resolutions.

Effect of IV Administration of a Gadolinium-Based Contrast Agent on Breast Diffusion-Tensor Imaging.

OBJECTIVE. The purpose of this study was to quantify changes in diffusion-tensor imaging (DTI) parameters before and after IV administration of a gadolinium-based contrast agent (GBCA) and explore the influence of those parameters on breast cancer diagnosis. SUBJECTS AND METHODS. A prospective cohort of 26 women with BI-RADS categories 0, 4, 5, or 6 underwent 3-T breast MRI with sequential DTI before GBCA administration and immediately after. Quantitative image analysis using dedicated DTI software yielded parametric DTI maps of each directional diffusion coefficient (DDC), mean diffusivity, and maximal anisotropy of the lesions and normal tissue. The color maps were evaluated and the lesion DTI parameters were compared before and after GBCA administration using appropriate statistical tests. RESULTS. Of the cohort, 58% had cancer (13 infiltrating ductal carcinoma, two ductal carcinoma in situ) and 42% had benign or normal results. All breast cancers were visually detected in the DDC λ1 maps before and after GBCA administration. Mean cancer size derived from λ1 maps before GBCA administration was 15.3 mm (range, 3.3-72.3 mm), and was not statistically significantly different from the size derived after GBCA administration of 17.3 mm (range, 3.9-71.0 mm). After GBCA administration, the cancers exhibited statistically significantly lower DDCs, mean diffusivity, and b0 intensity (p < 0.05), and no change in maximal anisotropy compared with before GBCA administration, whereas these parameters in normal and benign lesions did not change significantly after GBCA administration. The mean AUC values before and after GBCA administration, ranging from 0.735 to 0.985 and from 0.867 to 0.990, respectively, were not statistically significantly different for all parameters aside from λ3. CONCLUSION. Diagnostic accuracy using DTI was equivalent before and after GBCA administration, despite a change in the values of the DTI parameters. However, the limitations in standardization of contrast enhancement implies that unenhanced diffusion measurements should be preferred.

Resting-State Activity in High-Order Visual Areas as a Window into Natural Human Brain Activations.

A major limitation of conventional human brain research has been its basis in highly artificial laboratory experiments. Due to technical constraints, little is known about the nature of cortical activations during ecological real life. We have previously proposed the "spontaneous trait reactivation (STR)" hypothesis arguing that resting-state patterns, which emerge spontaneously in the absence of external stimulus, reflect the statistics of habitual cortical activations during real life. Therefore, these patterns can serve as a window into daily life cortical activity. A straightforward prediction of this hypothesis is that spontaneous patterns should preferentially correlate to patterns generated by naturalistic stimuli compared with artificial ones. Here we targeted high-level category-selective visual areas and tested this prediction by comparing BOLD functional connectivity patterns formed during rest to patterns formed in response to naturalistic stimuli, as well as to more artificial category-selective, dynamic stimuli. Our results revealed a significant correlation between the resting-state patterns and functional connectivity patterns generated by naturalistic stimuli. Furthermore, the correlations to naturalistic stimuli were significantly higher than those found between resting-state patterns and those generated by artificial control stimuli. These findings provide evidence of a stringent link between spontaneous patterns and the activation patterns during natural vision.

Noncontrast Breast MRI During Pregnancy Using Diffusion Tensor Imaging: A Feasibility Study.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is often a delayed diagnosis and contrast-enhanced MRI is contraindicated because gadolinium agents are known to cross the placenta. PURPOSE: To investigate the feasibility and clinical utility of noncontrast breast MRI using diffusion tensor imaging (DTI) in the diagnostic workup of PABC. STUDY TYPE: Prospective. POPULATION: Between November 2016 and January 2018, 25 pregnant participants (median gestational age: 17 weeks) were recruited from eight referral breast-care centers nationwide. Imaging indications included: newly-diagnosed PABC (n = 10, with 11 lesions), palpable mass/mastitis (n = 4), high-risk screening (n = 10), and monitoring neoadjuvant-chemotherapy response (n = 1). FIELD STRENGTH/SEQUENCE: 1.5T, T2 -weighted, and DTI sequences, prone position, with a scan duration of ∼12 minutes. ASSESSMENT: DTI parametric maps were generated and analyzed at pixel resolution, with reference to ultrasound (US) and pathology. STATISTICAL TESTS: Two-tailed Student's t-test was applied for evaluating differences between DTI parameters of PABC vs. healthy fibroglandular tissue. Pearson's correlation test was applied to measure the agreements between λ1-based longest tumor diameter, US, and pathology. RESULTS: All scans were technically completed and reached diagnostic quality, except one with notable motion artifacts due to positional discomfort, which was excluded. Nine out of 11 known PABC lesions and one newly-diagnosed lesion were visible on λ1, λ2, λ3, mean diffusivity (MD), and λ1-λ3 maps, with substantial parametric contrast compared with the apparently normal contralateral fibroglandular tissue (P < 0.001 for all). Two lesions of 0.7 cm were not depicted by the diffusivity maps. Tumor diameter measured on a thresholded λ1 map correlated well with US (r = 0.97) and pathology (r = 0.95). Malignancy was excluded by DTI parametric maps in scans of symptomatic and high-risk patients, in agreement with US follow-up, except for one false-positive case. DATA CONCLUSION: Noncontrast breast MRI is feasible and well-tolerated during pregnancy. Further studies with a larger and homogeneous cohort are required to validate DTI's additive diagnostic value, albeit this study suggests a potential adjunct role for this noninvasive approach in breast evaluation during pregnancy. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:508-517.

Quenching of spontaneous fluctuations by attention in human visual cortex.

In the absence of a task, the human brain enters a mode of slow spontaneous fluctuations. A fundamental, unresolved question is whether these fluctuations are ongoing and thus persist during task engagement, or alternatively, are quenched and replaced by task-related activations. Here, we examined this issue in the human visual cortex, using fMRI. Participants were asked to either perform a recognition task of randomly appearing face and non-face targets (attended condition) or watch them passively (unattended condition). Importantly, in approximately half of the trials, all sensory stimuli were absent. Our results show that even in the absence of stimuli, spontaneous fluctuations were suppressed by attention. The effect occurred in early visual cortex as well as in fronto-parietal attention network regions. During unattended trials, the activity fluctuations were negatively linked to pupil diameter, arguing against attentional fluctuations as underlying the effect. The results demonstrate that spontaneous fluctuations do not remain unchanged with task performance, but are rather modulated according to behavioral and cognitive demands.

Quantitative evaluation of breast cancer response to neoadjuvant chemotherapy by diffusion tensor imaging: Initial results.

BACKGROUND: Diffusion tensor imaging (DTI) yields several parameters that have not been tested in response evaluation to neoadjuvant chemotherapy (NAC). PURPOSE: To evaluate and compare in reference to histopathology findings the ability of DTI and dynamic contrast-enhanced (DCE) MRI to monitor response to NAC. STUDY TYPE: Retrospective. POPULATION: Twenty patients treated with neoadjuvant chemotherapy. FIELD STRENGTH/SEQUENCE: 1.5T MRI axial, bilateral T2 -weighted, DTI, and DCE-MRI. ASSESSMENT: A standardized blinded image analysis at pixel resolution generated color-coded maps of DTI and DCE parameters STATISTICAL TESTS: Pearson's correlation analysis and Bland-Altman plots of the DTI and DCE size changes and of the pathological final residual tumor diameter and DCE or DTI final diameter, from pre- to post-NAC. Spearman coefficient of rank correlation between the DTI and DCE size changes from pre- to post-NAC and Miller and Payne (M&P) pathological response grading. Receiver operating characteristic curve analyses to differentiate between responders to nonresponders on the basis of the DTI and DCE percent size changes and the changes in DTI parameters. RESULTS: DTI and DCE changes in the cancers' diameter and volume from pre- to post-NAC exhibited high and significant Pearson correlation (r = 0.82 P = 1.2 × 10-5 ). The DTI volume changes exhibited a significant Spearman coefficient rank correlation (0.68, P = 0.001) with the pathological M&P grading and differentiated between responders and nonresponders with area-under-the-curve (AUC) of 0.83 ± 0.10. A similar AUC for differentiating responders from nonresponders was exhibited by the changes in the highest diffusion coefficient (0.84 ± 0.11) and the mean diffusivity (0.83 ± 0.11). The DTI residual-tumor-diameter showed a high and significant Pearson correlation (r = 0.87 P = 1.2 × 10-6 ) to pathology tumor diameter. DATA CONCLUSION: DTI monitors changes in cancer size and diffusion tensor parameters in response to NAC with an accuracy equivalent to that of DCE, enabling differentiation of responders from nonresponders and assessment of residual tumor size in high congruence with pathology. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1080-1090.

Monitoring In-Vivo the Mammary Gland Microstructure during Morphogenesis from Lactation to Post-Weaning Using Diffusion Tensor MRI.

Lactation and the return to the pre-conception state during post-weaning are regulated by hormonal induced processes that modify the microstructure of the mammary gland, leading to changes in the features of the ductal / glandular tissue, the stroma and the fat tissue. These changes create a challenge in the radiological workup of breast disorder during lactation and early post-weaning. Here we present non-invasive MRI protocols designed to record in vivo high spatial resolution, T2-weighted images and diffusion tensor images of the entire mammary gland. Advanced imaging processing tools enabled tracking the changes in the anatomical and microstructural features of the mammary gland from the time of lactation to post-weaning. Specifically, by using diffusion tensor imaging (DTI) it was possible to quantitatively distinguish between the ductal / glandular tissue distention during lactation and the post-weaning involution. The application of the T2-weighted imaging and DTI is completely safe, non-invasive and uses intrinsic contrast based on differences in transverse relaxation rates and water diffusion rates in various directions, respectively. This study provides a basis for further in-vivo monitoring of changes during the mammary developmental stages, as well as identifying changes due to malignant transformation in patients with pregnancy associated breast cancer (PABC).

Removing silicone artifacts in diffusion-weighted breast MRI by means of shift-resolved spatiotemporally encoding.

PURPOSE: Evaluate the usefulness of diffusion-weighted spatiotemporally encoded (SPEN) methods to obtain apparent diffusion coefficient (ADC) maps of fibroglandular human breast tissue, in the presence of silicone implants. METHODS: Seven healthy volunteers with breast augmentation were scanned at 3 Tesla (T) using customized SPEN sequences yielding separate silicone and water (1) H images in one scan, together with their corresponding diffusion-weightings. RESULTS: SPEN's ability to deliver multiple spectrally resolved images in a single scan, coupled to the method's substantial robustness to magnetic field heterogeneities, served to acquire ADC maps that could be freed from contributions that did not belong to fibroglandular tissue. CONCLUSION: SPEN-based sequences incorporating spectral discrimination and diffusion-weighting enable the acquisition of reliable ADC maps despite the presence of dominant signals from silicone implants, thereby opening new screening possibilities for the identification of malignancies in breast augmented patients.

Can diffusion tensor anisotropy indices assist in breast cancer detection?

PURPOSE: To evaluate whether the various anisotropy indices derived from breast diffusion tensor imaging (DTI) can characterize the healthy breast structure and differentiate cancer from normal breast tissue. MATERIALS AND METHODS: Six healthy volunteers and retrospectively selected 24 breast cancer patients were imaged at 3T. DTI included two b-values 0 and 700 sec/mm2 with 20-64 gradient directions and TE of 120 or 90 msec. The normalized anisotropy indices: fractional anisotropy (FA), relative anisotropy (RA), and 1-volume ratio (1-VR), as well as the absolute maximal anisotropy index (λ1 -λ3 ) were compared. RESULTS: The spatial distribution of the various anisotropy indices in healthy volunteers exhibited a high congruence (Pearson correlation coefficients range: 0.79-1.0). All indices showed a statistically significant reduction (P < 0.001) following shortening of the diffusion time. Significantly lower λ1 -λ3 values were found in cancers as compared to normal breast tissue (P < 6.0 × 10-7 ), while the values of the normalized indices in cancers were not significantly different from those in normal breast tissue (P < 0.65 for FA, P < 0.6 for RA, and P < 0.2 for 1-VR). The contrast-to-noise ratio of λ1 -λ3 was significantly higher (P < 0.001) than those of the normalized anisotropy indices, and the area under the curve in a receiver operating characteristic analysis exhibited the highest value for λ1 -λ3 (0.89 ± 0.04 vs. 0.51-0.54 for the other anisotropy indices). CONCLUSION: Water diffusion anisotropy in the healthy breast can be similarly mapped by the normalized indices and by λ1 -λ3 . However, the normalized anisotropy indices fail to differentiate cancer from normal breast tissue, whereas λ1 -λ3 can assist in differentiating cancer from normal breast tissue. J. Magn. Reson. Imaging 2016;44:1624-1632.

Overcoming limitations in diffusion-weighted MRI of breast by spatio-temporal encoding.

PURPOSE: Evaluating the usefulness of diffusion-weighted spatio-temporal encoding (SPEN) methods to provide quantitative apparent diffusion coefficient (ADC)-based characterizations of healthy and malignant human breast tissues, in comparison with results obtained using techniques based on spin-echo echo planar imaging (SE-EPI). METHODS: Twelve healthy volunteers and six breast cancer patients were scanned at 3T using scanner-supplied diffusion-weighted imaging EPI sequences, as well as two fully refocused SPEN variants programmed in-house. Suitable codes were written to process the data, including calculations of the actual b-values and retrieval of the ADC maps. RESULTS: Systematically better images were afforded by the SPEN scans, with negligible geometrical distortions and markedly weaker ghosting artifacts arising from either fat tissues or from strongly emitting areas such as cysts. SPEN-derived images provided improved characterizations of the fibroglandular tissues and of the lesions' contours. When translated into the calculation of the ADC maps, there were no significant differences between the mean ADCs derived from SPEN and SE-EPI: if reliable images were available, both techniques showed that ADCs decreased by nearly two-fold in the malignant lesion areas. CONCLUSION: SPEN-based sequences yielded diffusion-weighted breast images with minimal artifacts and distortions, enabling the calculation of improved ADC maps and the identification of decreased ADCs in malignant regions.

Diffusion-tensor MR imaging of the breast: hormonal regulation.

PURPOSE: To investigate the parameters obtained with magnetic resonance (MR) diffusion-tensor imaging (DTI) of the breast throughout the menstrual cycle phases, during lactation, and after menopause, with and without hormone replacement therapy (HRT). MATERIALS AND METHODS: All protocols were approved by the internal review board, and signed informed consent was obtained from all participants. Forty-five healthy volunteers underwent imaging by using T2-weighted and DTI MR sequences at 3 T. Premenopausal volunteers (n = 16) underwent imaging weekly, four times during one menstrual cycle. Postmenopausal volunteers (n = 19) and lactating volunteers (n = 10) underwent imaging once. The principal diffusion coefficients (λ1, λ2, and λ3), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and maximal anisotropy (λ1-λ3) were calculated pixel by pixel for the fibroglandular tissue in the entire breast. RESULTS: In all premenopausal volunteers, the DTI parameters exhibited high repeatability, remaining almost equal along the menstrual cycle, with a low mean within-subject coefficient of variance of λ1, λ2, λ3, and ADC (1%-2% for all) and FA (5%), as well as a high intraclass correlation of 0.92-0.98. The diffusion coefficients were significantly lower (a) in the group without HRT use as compared with the group with HRT use (P < .01) and premenopausal volunteers (P < .01) and (b) in the lactating volunteers as compared with the premenopausal volunteers (P < .005). No significant differences in DTI parameters were found between premenopausal volunteers free of oral contraceptives and those who used oral contraceptives (P = .28-0.82) and between premenopausal volunteers and postmenopausal volunteers who used HRT (P = .31-0.93). CONCLUSION: DTI parameters are not sensitive to menstrual cycle changes, while menopause, long-term HRT, and presence of milk in lactating women affected the DTI parameters. Therefore, the timing for performing breast DTI is not restricted throughout the menstrual cycle, whereas the modulations in diffusion parameters due to HRT and lactation should be taken into account in DTI evaluation.