key: cord-0030051-57mdbl5y
authors: Nissan, Noam; Bauer, Ethan; Moss Massasa, Efi Efraim; Sklair-Levy, Miri
title: Breast MRI during pregnancy and lactation: clinical challenges and technical advances
date: 2022-04-09
journal: Insights Imaging
DOI: 10.1186/s13244-022-01214-7
sha: 670413aba61e8dfd8e253f3c82bb182b9fb389ee
doc_id: 30051
cord_uid: 57mdbl5y

The breast experiences substantial changes in morphology and function during pregnancy and lactation which affects its imaging properties and may reduce the visibility of a concurrent pathological process. The high incidence of benign gestational-related entities may further add complexity to the clinical and radiological evaluation of the breast during the period. Consequently, pregnancy-associated breast cancer (PABC) is often a delayed diagnosis and carries a poor prognosis. This state-of-the-art pictorial review illustrates how despite currently being underutilized, technical advances and new clinical evidence support the use of unenhanced breast MRI during pregnancy and both unenhanced and dynamic-contrast enhanced (DCE) during lactation, to serve as effective supplementary modalities in the diagnostic work-up of PABC.

• Diffusion MRI may serve as a standalone modality during pregnancy. • DCE MRI of the breast remains of significant value during lactation. • Unenhanced DTI may increase PABC lesion conspicuity as compared with DCE. • Non-fat suppressed T2 images can improve the delineating of non-mass DCIS lesions. • Increased utilization of MRI may facilitate an earlier PABC diagnosis.

Pregnancy-associated breast cancer (PABC) is traditionally defined as breast cancer diagnosed during pregnancy, in the first year postpartum, or anytime during lactation [1] , and typically represents a high-grade luminal b-like invasive ductal carcinoma [2] . Although it is a rare circumstance, occurring in 0.3 in 1000 pregnancies [3] , breast cancer stands among the most common types of malignancies occurring during pregnancy and its incidence is on the rise in developed countries as more women delay childbearing [4, 5] . The diagnosis of PABC could be challenging because of the unique physiological changes that the breast undergoes [6] , which may mask a concurrent malignant transformation both clinically and radiologically, while also dictating restrictions on the imaging work-up [7] . Ultimately, PABC is more likely to be diagnosed with an advanced disease than non-pregnant patients [8] , and consequently, is associated with a poorer prognosis [9], being the most common cause of cancer-related mortality in gestational women and associated with a mortality rate that is 50% higher when compared to non-PABC [10]. Magnetic resonance imaging (MRI) and in particular, it's workhorse sequence, dynamic contrast-enhanced (DCE) MRI, continues to serve in the mainstay of breast cancer diagnostic workup [11] [12] [13] , and to expand in potential indications [14] [15] [16] , owing to its high sensitivity for breast cancer detection and its unparalleled negative predictive value compared with conventional imaging

Insights into Imaging [17] . In the general population, only the high costs and low availability are perhaps the main reasons to hold breast MRI from becoming widely used in screening. [18] . Nevertheless, despite its evident diagnostic superiority, inherent limitations of breast MRI surface during pregnancy and lactation, and as a result, restrictions are imposed on its utility [4, [19] [20] [21] . During pregnancy, DCE-MRI does not play a role in the diagnostic workup of the breast due to fetal safety concerns associated with gadolinium-based contrast agents [22] , which are known to cross the placenta [23] . During lactation, gadoliniumbased contrast is considered safe for administration [24] . Yet, breast DCE-MRI is considered controversial during lactation due to probable limited sensitivity caused by the increased characteristic background parenchymal enhancement (BPE), which may hinder suspicious finding [25] [26] [27] .

In recent years, the advent of promising preliminary investigations and emergence of advanced MRI protocols, such as the increased clinical employment of unenhanced diffusion-based MRI techniques [28] , has driven groups of radiologists and researchers to attempt to expand the role of breast MRI during pregnancy and lactation, with the hope to facilitate an earlier diagnosis of PABC. The aim of this pictorial article is to discuss and illustrate the latest developments of breast MRI during pregnancy and lactation. Variations in breast MRI manifestation due to the periodic physiological modifications are reviewed, as well as the MR imaging spectrum of common benign entities and PABC.

Throughout pregnancy, the breast undergoes a series of unique structural and functional alterations in preparation for its eventual biological role in lactation. Within this process, called lactogenesis, the mammary gland grows with developed glandular tissue at the expense of shrunken adipose and connective tissues [29] . Regulated by key hormones, lactogenesis is composed from two stages, which is necessary for the breast in order to synthesize and secrete milk [30] . Secretory initiation takes place in the second trimester of pregnancy. In the postpartum period, secretory activation, the second stage of lactogenesis, begins and is followed with milk secretion which is triggered by the fall of progesterone blood levels [31] . The colostrum is temporarily enriched with protein and electrolytes and following several days of breastfeeding, turns into a mature, lipid-rich, and stable mother's milk [32] .

Both clinical and radiological evaluation of the breast are influenced by the physiological changes during pregnancy and lactation. Clinically, breast examination can be challenging due to the enlarged size of the breasts, their tenderness, and especially their harder, more nodular consistency [33] . Imaging-wise, each of the various radiological modalities is hampered by the various changes in the breast properties. Owing to its harmless nature and excellent utility in focal evaluation of palpable findings [34] , there is consensus that US represents the most appropriate and thus, the first-line imaging modality for breast evaluation during pregnancy and lactation [35] . The role of mammography is relatively diminished during pregnancy and lactation due to the increased mammographic density of the breast parenchyma and concerns related to radiation exposure for the fetus [19] . It should be mentioned though, that in many centers, mammography is considered generally safe during pregnancy and lactation, since the radiation dose from a bilateral two view mammogram is < 3 mGy per view, equivalent to 7 weeks of background radiation [36] . The increased mammographic density (Fig. 1 ) may well reduce the sensitivity of screen-detected tumors [37] , although mammography may still be useful in the detection of suspicious micro-calcifications. Therefore, mammography serves as an adjunct to US [27] . During lactation, patients are advised to nurse or pump immediately before undergoing mammography in order to decrease parenchymal density related to retained milk [6] . Rarely, mammography can also exhibit a unique form of scattered microcalcifications, secondary to gestational (pregnancy) or secretory (lactation) hyperplasia, which may add further complexity for mammographic evaluation (Fig. 1) [38, 39] .

These physiological changes of the breast are also reflected on the various MRI pulse sequences. Since contrast enhanced breast MRI scans are not performed during pregnancy, reports on breast MRI of pregnant patients have been limited to examinations performed prior to elected abortion [40] or using unenhanced protocol [41] . Breast MRI studies of the lactating breast are more common and include both DCE, as well as unenhanced sequences [40, [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] . The main MRI features of the breast during pregnancy and lactation are increased fibroglandular tissue [47] and increased vascularity, which is manifested by marked BPE [40, 42, 43, [49] [50] [51] [52] and results in false positive coloring on DCE computer aided diagnosis (CAD) mapping (Fig. 2) .

Further characterization of the lactating breast has been afforded by additional MRI sequences. On MR spectroscopy, a total choline peak, an established breast cancer biomarker [53] , was evident in exams of most healthy lactating volunteers, thus limiting its clinical role in this population [44] . On diffusion-weighted imaging (DWI), the measured apparent diffusion coefficient (ADC) of the lactating breast was found to be decreased relative to normal values among premenopausal, non-lactating, and healthy volunteers. This phenomenon is most likely due to the increased viscosity of the lipid-rich milk [45] , although the ADC is still higher than the malignant spectrum of values [44, 45, 47, 48] .

Advanced diffusion MRI models were also used to investigate the unique features of the breast during pregnancy and lactation. Intra-voxel incoherent motion (IVIM), a bi-exponential diffusion model, is based on acquiring multiple diffusion weightings in the fast and slow regimes in order to separate the fast perfusionbased "pseudo-diffusion" component from the slow diffusion process [54] . Using IVIM analysis, the lactating breast, as anticipated, has shown to exhibit increased perfusion fraction [48] , due to the pronounced vascularity of the breast parenchyma [42] and the high metabolic demand during breastfeeding [55] . Another approach could be found in diffusion tensor imaging (DTI), which is based on applying diffusion gradients to characterize tissue microstructure. These gradients go in multiple directions in order to map spatial information of the diffusion hindrance and restriction that goes beyond cellular density [56] . DTI properties among healthy, pregnant examinees resembled the measurements among nonpregnant, premenopausal examinees, with relatively high values of diffusivity, as expected for dense breasts [41] . Besides decreased diffusivity, DTI studies of the lactating breast also reported reduced anisotropy [45, 46] , probably owing to the physiological transient increase in the diameter of the lactiferous ducts [57] . Furthermore, DTI has enabled the characterization of the underlying ductal-tree architecture of the lactating breast, as demonstrated by the diffusion Eigen-vectors mapping. This is clearly illustrated by the predominance of diffusivity directed to the nipple with "duct-like, " linear, and branching vectors of the first eigenvalue [30, 46, 58] (Fig. 3 ).

Benign entities account for the vast majority of findings among patients presenting with a palpable breast mass during pregnancy and lactation [6] . In a study that evaluated the diagnostic workup of 164 lesions among pregnant, lactating, and postpartum women, Robbins and co-authors reported that most of the cases appeared during lactation (65%), and breast cancer accounted for only 2.4% of cases (4/164), even though cancer constituted 10% of the eventual biopsies [59] . Benign conditions, however, are more common and are either the same as those observed in non-pregnant women [60] or breast abnormalities distinctive for pregnancy and lactation [61] . Examples of these mimickers include, though not exclusively, galactocele, lactating adenoma, fibroadenoma, duct ectasia, mastitis, and abscess [62] , along with common contemporary mimickers that affect breast imaging, such as vaccination induced lymphadenopathy [63] . Their presentation, with focus on their MRI Fig. 1 Changes in mammographic density and lactation-associated microcalcifications. Left breast medio-lateral-oblique view mammograms of the same patients, performed 2 years apart, prior to pregnancy (a) and during lactation (b) are presented, demonstrating the marked increase in breast volume and mammographic density associated with pregnancy and lactation. Additionally, new onset of lactation-associated microcalcifications was depicted globally on both breasts (b and zoomed image) characteristics, will be discussed below. In addition, a summary of the typical MRI features of the common breast lesions during pregnancy and lactation is provided in Table 1 .

A galactocele, a Greek term meaning "milky pouch, " is a milk collection retained within the fibroglandular tissue because of duct obstruction. This etiology usually regresses spontaneously on follow-up and is the most common benign breast mass among lactating patients [64] . Characterized with a cyst-like formation, a galactocele is often surrounded by a fibrous capsule with variable luminal morphology depending on the distribution of its contents: fat, protein and fluid [61] . Mostly encountered after cessation of breast-feeding, galactoceles can also be present earlier, occasionally even in the third trimester of pregnancy [6] . Similar to other pregnancyassociated breast lumps, the typical clinical manifestation is a painless, palpable mass, arising upon breastfeeding cessation [60] . From the imaging perspective, galactocele is mostly described according to its sonographic appearance [65] ; usually as round or oval in shape, with variable echogenicity which most likely increases as the lesion ages and a characteristic fat-fluid level [66] . MRI features of galactocele are hardly described in the literature, as US is sufficient for its diagnostic work-up. Recently, Rosas et al. provided MR images showing a cyst with a thin septa, heterogeneous content, and fat-fluid level, which is compatible with the diagnosis [19] (Fig. 4) . 

Lactating adenoma represents a benign stromal alteration with a tendency to regress upon breastfeeding cessation [67] . Lactating adenoma is the most prevalent breast lesion occurring during pregnancy, usually appearing during the third trimester or during lactation, as a painless, palpable, and mobile breast lump [68] . Typical US features of lactating adenoma favor a benign mass, including a solid, ovoid, well-defined, and wider-than-taller lesion with homogeneous and hypoechoic appearance alongside posterior acoustic enhancement [69] . On MRI, lactating adenoma has been described as fibroadenoma-like; a well circumscribed mass, containing hypointense septa, causing Note: a cyst with thin septa, heterogeneous content, and fat-fluid level is exhibited and compatible with galactocele diagnosis. Reproduced with permission from Radiologia Brasileira [19] mass effect by displacing the adjacent normal breast parenchyma and the main galactiferous ducts of the nipple-areolar complex [70] . Herein, we present another representative MRI case of a biopsy-confirmed lactating adenoma. Our findings suggest that lactating adenoma may exhibit benign features of enhancement kinetics on DCE MRI (Fig. 5) .

Fibroadenomas are composed of epithelium and stroma and account for the most common benign tumor detected in young females [71] . Interestingly, before pregnancy, fibroadenomas may remain latent and asymptomatic until becoming clinically apparent as a new-onset palpable mass after hormonally stimulated growth [6] . Clinically, fibroadenomas, which are often multiple and bilateral, usually present as a painless firm, mobile, and rubbery mass. Less frequently, fibroadenomas may experience a tremendous growth spurt, resulting in central infarction, and then becoming tender [72] . On mammography, fibroadenomas often appear as a well-defined round or oval mass which may also exhibit pathognomonic benign calcifications, making a further imaging work-up unnecessary [73] . On US, fibroadenomas among pregnant or lactating women is the same as among the general population, exhibiting a circumscribed, wider-than-taller oval or round mass [74] . Infarcted or complexed fibroadenomas may show suspicious features such as irregular margins and internal cystic changes that warrant biopsy [75] . On MRI, fibroadenomas usually exhibit a benign morphology on unenhanced sequences, including a sharp contour without signs of infiltration [76] . Additionally, they exhibit benign DCE patterns such as a persistent kinetic curve [77] and a high extracellular volume fraction with low to moderate microvascular permeability [78] . A representative case of a growing fibroadenoma is given in Fig. 6 .

Duct ectasia of the breast is among the benign processes that may affect the nipple-areolar complex during pregnancy and lactation [79] . The clinical course of duct ectasia ranges from asymptomatic to symptoms such as nipple discharge, nipple retraction, a palpable mass, and mastalgia [80] . Depending on the degree of dilatation as well as the mammographic density, duct ectasia may be visible at mammography as dense tubular structures converging on the nipple-areolar complex [81] . Sonographically, it appears as anechoic, smooth-walled, and branching structures that taper peripherally [82] . On MRI, the ductal structures may be visible on fat-suppressed T1 and T2-weighted images depending on if its contents are composed of protein or fluids, respectively. Despite being regarded as benign, a unilateral duct dilatation may be an indicator of malignancy and hence, the importance of its diagnostic work-up [83] . An illustrative case of duct ectasia mimicking malignancy is shown in Fig. 7 .

Mastitis is a common infectious condition that may affect up to one-third of lactating women [84] and is among the leading medical causes of premature breastfeeding cessation [85] . Among the most common complications are mastitis that are abscesses with a purulent collection. Its pathophysiology is thought to be related to transmission of oral bacterial from the infant to the mother's lactiferous ducts. Maternal risk factors that were identified include previous mastitis during breastfeeding, cesarean section, breast trauma, latch problems, milk , c) , below the signal intensity threshold for suspicious findings on CAD (d). Despite these benign features, the patient underwent vacuum-assisted biopsy which revealed lactating adenoma overproduction, blocked duct, and more [86] . Clinically, mastitis presents with focal mastalgia, edema, and erythema which may be accompanied fever and elevated blood test inflammatory markers. Focused US is indicated to rule out abscess when the infection is refractory to antibiotics, or for therapeutic guided-aspiration of the abscess [87] . Sonographically, it typically is characterized by an area of fluid collection with thin septations or debris, thickened walls, uncircumscribed margins and posterior acoustic enhancement [60] . With that regards, another related entity worth mentioning is granulomatous mastitis (GM), a rare benign inflammatory breast disease that affects mostly women of childbearing age with a history of breastfeeding and may mimic both abscess and carcinoma [88] . Breast MRI is not indicated during acute mastitis; however, when mastitis symptoms persist despite well-managed medical treatment, MRI may be performed. The main differential diagnosis of exclusion is inflammatory breast cancer [89] , notwithstanding overlapping enhancement features of the two entities [90] . Herein, we present two cases in which MRI was utilized during for mastitis evaluation (Fig. 8) and abscess monitoring (Fig. 9 ).

During pregnancy, breast DCE-MRI is contraindicated due to the increased risk of a broad set of rheumatological, inflammatory, or dermal conditions, as well as stillbirth or neonatal death, associated with gadoliniumbased contrast agents used during the MRI [22] . The lone report on breast DCE-MRI during pregnancy was composed of PABC patients who elected to undergo abortion [40] . Despite the lack of supportive evidence for improved maternal outcomes for pregnant breast cancer patients undergoing therapeutic abortion [91] , an elective abortion remains frequent in patients diagnosed in the first trimester [92] . In these patients, DCE-MRI can aid in improved pre-operative assessment, providing additional diagnostic information regarding tumor size, extent of disease and contralateral involvement compared to mammography and US, in up to 28% of cases [40] . A representative MRI of a pregnant breast cancer patient who elected to undergo abortion is given in Fig. 10 , showing the tumor extent superimposed on the notable pregnancy-associated BPE. Moreover, the first attempt to utilize unenhanced diffusion MRI as a standalone modality for pregnant patients at high risk or with newly diagnosed PABC was recently reported [37] . This work demonstrated the feasibility and tolerability of breast MRI in the prone position among pregnant patients, although most cases involved pregnant women in the first and second trimesters. In order to decrease any gravitational pressure from the belly, extra pillows were placed underneath the women to assist with pelvic lifting. In terms of diagnostic performance, diffusivity maps were useful in detecting nine out of 11 lesions and excluded malignancy in 14 highrisk patients; however, the maps were unable to detect two 7 mm lesions, as anticipated under the technical limitations of this modality [93] . Representative cases of unenhanced MRI in pregnant breast cancer patients are shown in Fig. 11 [94] , highlighting the potential diagnostic advantages of this approach.

An interesting and unusual case we encountered was of a pregnant patient with newly diagnosed mucinous breast carcinoma who underwent MRI prior to elected abortion. Pure mucinous carcinoma typically appears on MRI as a circumscribed mass with extremely high signal intensity on fat-saturated T2-weighted imaging and a benign-appearing persistent enhancement curve [94, 95] . As demonstrated in Fig. 12 , the palpable lesion on the left breast was not detected on DCE and CAD images because of concurrence of its benign-like kinetic features and the marked surrounding BPE. Yet, the lesions were clearly visible on fat-suppressed T2-weighted images, therefore stressing the importance of acquiring broad protocol in diagnostic breast MRI.

Unenhanced diffusion MRI is also gaining recognition in the diagnostic workup of PABC for the systemic staging of pregnant patients, when the use of PET/CT is discouraged [95] . For this purpose, a whole-body MRI relying on DWI with background suppression (DWIBS) sequence has been applied [96] . This emerging MRI technique can provide non-invasive information regarding the extent of disease and distant metastasis and often provides diagnostic value that changes the patient management [97, 98] .

Breast MRI is much more common during lactation, due to the fact that injection of gadolinium-based contrast agent is considered safe for administration [20] . Past studies evaluating the gadolinium excretion into breast milk revealed that less than 0.04% of the administered dose reaches the milk [99] , and, of that amount, only 0.8% is actually absorbed by the infant [100] . Accordingly, some authors openly assert that lactating patients should not be advised to suspend breastfeeding at all, given that the risks associated with interrupting breastfeeding outweigh the negligible amount of contrast media [101] . More conservative approaches suggest the option of abstaining from breastfeeding for a period of 12-24 h if this is the preference of an informed mother [102] .

Since the excretion of gadolinium to breast milk has been shown to reach its peak after approximately 4 h [103] , if lactating patients have concerns about breastfeeding, the authors advise to pump and dump the milk with continuation of nursing after 6 h. The main concern regarding the use of breast MRI during lactation does not stem from safety worries, but rather reservations regarding its uncertain diagnostic performance. In light of the increased BPE, there are concerns that it may potentially obscure the presence of the underlying tumor [27] . Several publications reported that despite increased surrounding BPE, high sensitivity was observed in known PABC cases that underwent DCE-MRI [40, [49] [50] [51] .

Herein, we present an assembly of representative cases, illustrating the spectrum of appearance and persevered diagnostic capabilities of breast MRI, even in lactating patients. The first case is a pre-operative MRI of a PABC patient who presented with a palpable mass after 3 months of lactation. IDC was diagnosed using US-guided biopsy, and MRI reassured the existence of a solitary lesion on top of the surrounding BPE (Fig. 13) . Occasionally, the diagnostic workup of known, newly diagnosed PABC can get complicated by simultaneous benign lactation-related findings, as shown by Fig. 14. In this patient, a preoperative MRI performed in a lactating patient revealed the known 2.8 cm IDC, as well as another enhancing 0.9 cm lesion which warranted focused US and biopsy to reveal adenosis and lactating changes on pathology. This case demonstrated that an argument regarding reduced specificity of breast MRI during lactation could be claimed.

One noteworthy type of cancer that deserves a specific mention is ductal carcinoma in situ (DCIS), which often displays overlapping radiological and pathological features with lesions with uncertain malignant behavior [104] . Unlike invasive carcinomas that tend to present as a mass, DCE-MRI usually depicts DCIS as non-mass enhancement (NME) with a larger median span than mammography [105] . Taking into consideration the difficulty in unravelling BPE from NME [106] , this casts doubt regarding the utility of breast MRI to detect DCIS during lactation could arise. Two representative newly diagnosed DCIS cases undergoing preoperative breast MRI during lactation are presented in Figs. 15 and 16 . Both patients presented with palpable mass and mammography detected suspicious linear micro-calcifications in typical segmental distribution. DCE-MRI displayed NME in the tumor region, enhancing more vividly than the surrounding lactation-induced BPE. Interestingly, additional diagnostic value was provided by non-fat suppressed T2-weighted images, allowing better depiction of lesion morphology and margins (Fig. 15 ). Occasionally, PABC can manifest as multi-centric carcinoma, which is difficult to fully estimate its extent using conventional imaging. A representative case of a lactating patient with newly diagnosed IDC which turned to comprise no less than seven distinct malignant ipsi-lateral lesions is presented in Fig. 17 , highlighting the ability of DCE-MRI, as well as unenhanced DWI to portray the entire extent of disease. With that regards, a recent comparative study investigated tumor conspicuity in DCE-MRI and unenhanced DTI protocol among lactating patients with PABC [51] . On DCE-MRI, because of the marked BPE, tumor conspicuity was reduced by 60% as compared to non-lactating controls. On the contrary, an additional 138% increase in tumor conspicuity on DTI compared with DCE was observed, underscoring a clear advantage for unenhanced MRI to operate in the setting of lactation-induced BPE.

Since PABC is often a delayed diagnosis, it is associated with more advanced tumor size at the time of diagnosis compared to non-PABC [107] and eventually may lead to increased rates of mastectomy as the treatment of choice [108] . Therefore, it is not uncommon to encounter a large PABC lesion occupying a high portion of the breast size, as demonstrated in Figs. 18 and 19 . These images show the complete extent of the enormous tumors which are clearly depicted on both DCE as well as on unenhanced DWI.

Unenhanced diffusion MRI during pregnancy. T2, DWI, and DTI parametric maps of three PABC patients (A-C). T2-weighted, DWI and DTI-derived diagnostic parametric maps of λ1, MD, and λ1-λ3 of three patients with newly diagnosed IDC are presented. The lesion appears bright on DWI (b 700 s/mm 2 ). Using the parametric threshold, the lesion could be easily depicted on l1, and MD maps, as well as on l1-l3 map, compared with the measurements in the normal tissue. Reproduced with permission from Journal of the American College of Radiology

Considering the difficulty of interpretation of DCE-MRI with marked BPE and the high likelihood of lactationrelated benign entities, some authors suggest that it may be reasonable to delay the examination until several months after weaning to minimize false-positive results that may lead to unnecessary biopsies [26] . Screening MRI was once recommended in the breastfeeding period for "women who are at very high-risk for breast cancer" [7], or within the first 6 months postpartum [109] . Others suggested waiting until 3 months after cessation of breastfeeding since the imaging changes should resolve by this time-span following lactation cessation [6] . Recently, the ACR guidelines recommended resuming MRI screening for patients over 30 years old if breastfeeding is continued for more than 6 months. Otherwise, the ACR recommends resuming annual high-risk screening MRI 6-8 weeks following cessation of breastfeeding [20] . All in all, despite the variance in the literature, based on our institutional experience, the authors advocate not to postpone pre-operative MRI of newly diagnosed lactating PABC patient. Usually, from the beginning of the diagnostic work-up and until pathological confirmation of the cancer, the patients often discontinue nursing, and even this interlude period of 1-2 weeks may be sufficient to decrease the level of BPE. Among patients who are diagnosed with breast cancer post-weaning, lactation-related BPE is no longer expected and the tumor can be clearly viewed by DCE (Fig. 20) .

In light of the marked physiological changes that the breast undergoes during pregnancy and lactation, clinical and radiological evaluation of the breast becomes extremely challenging. Considering the high incidence of gestational-associated benign breast entities, it is no surprise that PABC is often a delayed diagnosis [110] . The delay could be attributed to either the patient, if they postpone seeking medical evaluation, the physician, if they provide a false-negative clinical assessment of the symptomatic breast, or an imaging-related delay, via a false-negative radiological evaluation [111] . Ultimately, PABC is typically diagnosed only after clinical symptoms arise, most commonly as a large palpable mass [112] . Considering that PABC's prognosis is not inferior from that of non-PABC when adjusted for stage and age [113] , it appears that the delay in diagnosis, rather than the gestational state and associated overexpressed vascular, hormonal and growth-factor mediators [114] , is responsible for its poor prognosis. This demonstrates the unmet need to adapt new screening strategies for high-risk populations during this period [20, 109] , as well as to develop and utilize advanced imaging tools for achieving early diagnosis.

While there is wide agreement that US should be the first-line modality for breast imaging during pregnancy and lactation, and that mammography may have a supplementary additive role, the role of MRI remains controversial in the diagnostic work-up of PABC. In this pictorial review, we have illustrated how gestationalrelated physiological and benign processes are translated to MRI. Moreover, we have demonstrated the promising utility of unenhanced MRI to serve as a standalone breast imaging modality during pregnancy, and the more established utility of both contrast enhanced and unenhanced breast MRI during lactation. Specifically, it appears that since most cases of PABC reach the radiological work-up with a large palpable mass, the opportunity to facilitate an earlier diagnosis of PABC could be found among highrisk patients and BRCA mutation carriers, which account for up to 35% of PABC cases [115] . In this population, action should be taken to investigate whether screening MRI can detect PABC with asymptomatic disease.

Unenhanced breast MRI using DWI variants has shown great strides to serve as a possible cost-effective, fast, and clinically effective alternative to DCE [116] . Nevertheless, several factors are still holding it from being fully integrated into daily practice [117] . Technically, breast DWI is prone to eddy currents, geometrical and intensity distortions, and echo planar Yet, additional ipsi-lateral enhancing 0.9 cm lesion is apparent (b). Upon focused US and US-guided biopsy, the second lesion came up to be adenosis and lactating changes on pathology. Interestingly, CAD depicted both lesions, as well as slight BPE in blue color, which corresponds to persistence wash-in pattern which usually represents a benign pattern (c) imaging ghosts artifacts [93] . Clinically, lower sensitivity of breast DWI was noted in cases of sub-centimeter lesions [118, 119] , as well as in NME lesions [120] . To overcome these drawbacks, several strategies were recently attempted in order to provide robustness to artifacts and improve image quality [121] [122] [123] [124] [125] . Spatial resolution was also improved by reaching up to sub-millimeter pixel resolution [126] [127] [128] , eventually allowing for visibility of higher lesions [129] and greater morphological concordance between DWI and DCE [130] . Thus, the authors foresee an encouraging future for breast DWI in general, and in particular with PABC.

For DCE, it is safe to assume that during pregnancy it would remain unutilized. During lactation, however, the role of DCE may expand, possibly due to the implementation of novel acquisition schemes that may allow better separation between enhancing lesions and BPE. In recent years, developments in accelerated MRI using the application of compressed sensing [131] have allowed the faster acquisition of MRI data. This relies on exploiting sparsely under-sampled k-space in peripheral regions while continuously sampling the k-space center to enable high temporal resolution with preserved spatial resolution. Several sparse methods have been integrated to MRI protocols, including time-resolved angiography with stochastic trajectory (TWIST) [132] and golden-angle radial sparse parallel (GRASP) [133] . Optimization of sparse techniques to breast MRI has promoted the novel approach of ultrafast DCE with temporal resolution of less than 10 s during the initial wash-in phase, compared with a standard temporal resolution of up to 2 min in conventional MRI [134] . Analysis of the wash-in kinetics has been found to provide valuable information for lesion characterization [134] [135] [136] [137] [138] [139] and since BPE usually exhibits slow early enhancement slope and persistent delayed enhancement [140] , ultrafast sequence might therefore be suitable for early visualization of malignant lesions with minimization of lactation-induced BPE [141] . The accumulation of BPE along the early phases of wash-in during ultrafast breast DCE of healthy lactating patients is demonstrated in Fig. 21 . Altogether, there is a clinical necessity of further studies on larger cohort of patients to evaluate the role of breast MRI during pregnancy and lactation, and in particular as a screening tool among high-risk populations during this period.

During pregnancy and lactation, the breast experiences substantial changes in morphology and function that affect its imaging properties and may reduce the visibility of concurrent pathological processes. Moreover, the high incidence of benign, gestational-related entities may further add complexity to the clinical and radiological evaluation of the breast during this period. Consequently, PABC is often a delayed diagnosis that carries a poor prognosis. Despite currently being underutilized, this state-of-the-art pictorial review illustrates how technical advances and new clinical evidence support the use of unenhanced breast MRI during pregnancy and both unenhanced and DCE during lactation. These modalities serve as effective supplementary options in the diagnostic work-up of PABC, especially among high risk populations, with the aim to facilitate an earlier diagnosis. Ultrafast DCE-MRI of the lactating breast. Subtracted ultrafast DCE-MRI of the right breast of a healthy lactating patient (34 years old, lactation duration 18 months) are presented. Using grasp-vibe, a compressed-sensing technique, acquisition of ten consecutive T1-weighted images in the first minute post injection was enabled. Note: the prominent lactation-induced BPE (grade 3) appears only in the fifth acquired T1 image, approximately after 30 s, and further enhances in the following phases

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Intravoxel incoherent motion (IVIM) and non-Gaussian diffusion MRI of the lactating breast

MR imaging characteristics of breast cancer diagnosed during lactation

Background parenchymal enhancement in pregnancy-associated breast cancer: A hindrance to diagnosis?

Breast MRI during lactation: effects on tumor conspicuity using dynamic contrast-enhanced (DCE) in comparison with diffusion tensor imaging (DTI) parametric maps

MRI of the lactating breast : computer-aided diagnosis false positive rates and background parenchymal enhancement kinetic features

In vivo MR spectroscopy for breast cancer diagnosis

Clinical intravoxel incoherent motion and diffusion MR imaging: past, present, and future

Physiologic and hypermetabolic breast 18-F FDG uptake on PET/CT during lactation

Diffusion tensor imaging: concepts and applications

Ultrasound imaging of the lactating breast: Methodology and application

Robust diffusion tensor imaging by spatiotemporal encoding: principles and in vivo demonstrations

Accuracy of diagnostic mammography and breast ultrasound during pregnancy and lactation

Radiologic evaluation of breast disorders related to pregnancy and lactation

Spectrum of pregnancy-and lactation-related benign breast findings

Mimickers of breast malignancy: imaging findings, pathologic concordance and clinical management. Insights Imaging

COVID-19 vaccination induced lymphadenopathy in a specialized breast imaging clinic in Israel: analysis of 163 cases

Imaging and management of breast masses during pregnancy and lactation

Imaging of fat-containing lesions of the breast: a pictorial essay

Sonographic appearances of galactoceles

Lactating adenoma: US features and literature review

Five-year study of patients with lactating adenoma and review of the five-year study of patients with lactating adenoma and review of the literature

Imaging of lactating adenoma: differential diagnosis of solid mass lesion in a lactating woman

Early onset lactating adenoma and the role of breast MRI: a case report

Clinical expert series benign breast disease

Infarcted fibroadenoma of the breast: report of two new cases with review of the literature

Fibrous lesions of the breast: imaging-pathologic correlation

Diagnosis and treatment of breast fibroadenomas by ultrasound-guided vacuum-assisted biopsy

Incidence and management of complex fibroadenomas

The variability of fibroadenoma in contrast-enhanced dynamic MR mammography

Computer-aided detection (CAD) for breast MRI: evaluation of efficacy at 3.0 T

Breast fibroadenoma: mapping of pathophysiologic features with three-time-point, contrast-enhanced MR imaging-pilot study. Radiology

The management of breast symptoms in the pregnant and lactating patient

Sonographic findings of mammary duct ectasia: can malignancy be differentiated from benign disease

Multimodality approach to the nipple-areolar complex: a pictorial review and diagnostic algorithm. Insights Imaging

Common and unusual diseases of the nipple-areolar complex

Asymmetric ductal ectasia: an often overlooked sign of malignancy

Case-control study of risk factors for infectious mastitis in Spanish breastfeeding women

Occurrence of lactational mastitis and medical management: a prospective cohort study in Glasgow

Maternal risk factors for lactation mastitis: a meta-analysis

Management of mastitis in breastfeeding women

Granulomatous mastitis: a therapeutic and diagnostic challenge

Breast inflammation: indications for MRI and PET-CT

MRI of the breast in the differential diagnosis of mastitis versus inflammatory carcinoma and follow-up

Treatment of the pregnant mother with cancer: A systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part I: Solid tumors

Incidence of pregnancy-associated cancer in Denmark

Advantages and drawbacks of breast DTI

Breast MRI without contrast is feasible and appropriate during pregnancy

Gynaecological cancers in pregnancy

Fast and noninvasive characterization of suspicious lesions detected at breast cancer X-ray screening: capability of diffusion-weighted MR imaging with MIPs

Whole body MRI for systemic staging of breast cancer in pregnant women

Feasibility of whole-body diffusion-weighted MRI for detection of primary tumour, nodal and distant metastases in women with cancer during pregnancy: a pilot study

Gadopentetate dimeglumine excretion into human breast milk during lactation

Quantitative analysis of gadopentetate dimeglumine excreted in breast milk

Breastfeeding and radiologic procedures

Excretion of gadopentetate dimeglumine in human breast milk

High-risk lesions of the breast: concurrent diagnostic tools and management recommendations

Preoperative breast MRI for newly diagnosed ductal carcinoma in situ: imaging features and performance in a multicenter setting (ECOG-ACRIN E4112 trial). Radiology

Revisiting nonmass enhancement in breast MRI: analysis of outcomes and follow-up using the updated BI-RADS atlas

Tumor characteristics and prognosis in women with pregnancy-associated breast cancer

Breast cancer screening in high-risk patients during pregnancy and breastfeeding: a systematic review of the literature

Reducing delay in the diagnosis of pregnancy-associated breast cancer: how imaging can help us

Clinical presentation and causes of the delayed diagnosis of breast cancer in patients with pregnancy associated breast cancer

A single-institution study of 117 pregnancy-associated breast cancers (pabc): presentation, imaging, clinicopathological data and outcome

Prognosis of women with primary breast cancer diagnosed during pregnancy: results from an international collaborative study

Pregnancy and breast cancer: pathways to understand risk and prevention

Germline mutations in a clinic-based series of pregnancy associated breast cancer patients

Diffusion-weighted imaging of the breast: current status as an imaging biomarker and future role

Factors affecting the value of diffusion-weighted imaging for identifying breast cancer patients with pathological complete response on neoadjuvant systemic therapy: a systematic review

Diffusion-weighted MRI as an adjunct to mammography in women under 50 years of age: an initial study

Diffusion-weighted imaging with apparent diffusion coefficient mapping for breast cancer detection as a stand-alone parameter: comparison with dynamic contrast-enhanced and multiparametric magnetic resonance imaging

Limited role of DWI with apparent diffusion coefficient mapping in breast lesions presenting as non-mass enhancement on dynamic contrast-enhanced MRI

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

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

Multishot diffusion-weighted MRI of the breast with multiplexed sensitivity encoding (MUSE) and shot locally low-rank (shot-LLR) reconstructions

Correction of artifacts induced by B0 inhomogeneities in breast MRI using reduced-fieldof-view echo-planar imaging and enhanced reversed polarity gradient method

Distortion correction in diffusion-weighted imaging of the breast: performance assessment of prospective, retrospective, and combined (prospective + retrospective) approaches

Bilateral diffusion-weighted MR imaging of breast tumors with submillimeter resolution using readoutsegmented echo-planar imaging at 7 T

A comparison of methods for high-spatial-resolution diffusion-weighted imaging in breast MRI

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

Comparison of simultaneous multi-slice single-shot DWI to readout-segmented DWI for evaluation of breast lesions at 3T MRI

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

Sparse MRI: the application of compressed sensing for rapid MR imaging

Application of time-resolved angiography with stochastic trajectories (TWIST)-Dixon in dynamic contrast-enhanced (DCE) breast MRI

XD-GRASP: Golden-angle radial MRI with reconstruction of extra motion-state dimensions using compressed sensing

A novel approach to contrast-enhanced breast magnetic resonance imaging for screening: high-resolution ultrafast dynamic imaging

Maximum slope of ultrafast dynamic contrast-enhanced MRI of the breast: comparisons with prognostic factors of breast cancer

Compressed sensing for breast MRI: resolving the trade-off between spatial and temporal resolution

Maximum slope using ultrafast breast DCE-MRI at 1.5 Tesla: a potential tool for predicting breast lesion aggressiveness

Ultrafast dynamic contrast-enhanced breast MRI may generate prognostic imaging markers of breast cancer

Abbreviated breast magnetic resonance protocol: value of high-resolution temporal dynamic sequence to improve lesion characterization

Background parenchymal enhancement and uptake as breast cancer imaging biomarkers: a state-of-the-art review

Abbreviated MR imaging for breast cancer

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