Functional hemodynamic imaging markers for the prediction of pathological outcomes in breast cancer patients treated with neoadjuvant chemotherapy.

Significance: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes. Aim: We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT. Approach: Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers. Results: Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles (p=0.042). In addition, the change in normalized tumor StO2 upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle (p=0.038). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI. Conclusions: These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens.

Breast imaging with an ultra-low field MRI scanner: a pilot study.

Breast cancer screening is necessary to reduce mortality due to undetected breast cancer. Current methods have limitations, and as a result many women forego regular screening. Magnetic resonance imaging (MRI) can overcome most of these limitations, but access to conventional MRI is not widely available for routine annual screening. Here, we used an MRI scanner operating at ultra-low field (ULF) to image the left breasts of 11 women (mean age, 35 years ±13 years) in the prone position. Three breast radiologists reviewed the imaging and were able to discern the breast outline and distinguish fibroglandular tissue (FGT) from intramammary adipose tissue. Additionally, the expert readers agreed on their assessment of the breast tissue pattern including fatty, scattered FGT, heterogeneous FGT, and extreme FGT. This preliminary work demonstrates that ULF breast MRI is feasible and may be a potential option for comfortable, widely deployable, and low-cost breast cancer diagnosis and screening.

Method to improve the localization accuracy and contrast recovery of lesions in separately acquired X-ray and diffuse optical tomographic breast imaging.

Near-infrared diffuse optical tomography (DOT) has the potential to improve the accuracy of breast cancer diagnosis and aid in monitoring the response of breast tumors to chemotherapy by providing hemoglobin-based functional imaging. The use of structural lesion priors derived from clinical breast imaging methods, such as mammography, can improve recovery of tumor optical contrast; however, accurate lesion prior placement is essential to take full advantage of prior-guided DOT image reconstruction. Simultaneous optical and anatomical imaging may not always be possible or desired, which can make the accurate registration of the lesion prior challenging. In this paper, we present a three-step lesion prior scanning approach to facilitate improved accuracy in lesion localization based on the optical contrast quantified by the total hemoglobin concentration (HbT) for non-simultaneous multimodal DOT and digital breast tomosynthesis (DBT) imaging. In three challenging breast cancer patient cases, where no clear optical contrast was present initially, we have demonstrated consistent improvement in the recovered HbT lesion contrast by utilizing this method.

Axillary Ultrasound Evaluation in Breast Cancer Patients: A Multidisciplinary Viewpoint and Middle Ground.

Over the past decade, there has been a trend toward de-escalation of axillary surgery. Certain patients may now forego axillary lymph node dissection even in the setting of a positive sentinel lymph node biopsy (SLNB), and some patients may not even undergo a SLNB. However, there is wide variability in the imaging approach to assessing axillary lymph nodes in patients with breast cancer. Approaches range from performing axillary US in all patients with newly diagnosed breast cancer to omitting axillary imaging evaluation in all patients. This article provides a multidisciplinary middle ground approach for axillary nodal evaluation. The clinical impact and rationale for appropriate axillary nodal imaging are discussed and an imaging algorithm is proposed.

Imaging Evaluation of the Axilla-A National Survey of Clinical Practice Among Radiologists.

OBJECTIVE: To assess awareness and implementation of the American College of Surgeons Oncology Group Z0011 trial findings, approaches to axillary nodal imaging, and to identify differences in practice based on respondent characteristics. METHODS: An online survey was distributed to members of the Society of Breast Imaging. Questions regarded demographics, evaluation approaches, and impact of the Z0011 trial. Poisson regression with robust standard errors to regression was used to generate multivariable-adjusted relative risks and 95% confidence intervals (CIs) for associations. RESULTS: The response rate was 21.7% (430/2007). The majority (295/430, 68.6%) reported always performing axillary US in patients with a BI-RADS 4B, 4C, or 5 breast mass. Most respondents (299/430, 69.5%) were familiar with the findings of the Z0011 trial. Radiologists in academic practice were 0.67 (95% CI: 0.54-0.83) times less likely than private practice radiologists to perform axillary US in all masses and 1.31 (95% CI: 1.13-1.52) times more likely to be very familiar with the trial. Frequency of axillary US showed no association with time spent in breast imaging, years in practice, or presence of dedicated breast surgeons. Increased time in breast imaging and presence of dedicated breast surgeons was strongly associated with familiarity with the trial. No association was observed with years in practice. Most respondents (291/430, 67.7%) made little or no change to their practice based on trial findings. CONCLUSION: There is wide variability in approaches to axillary nodal evaluation, demonstrating a need for improved education and guidelines for axillary imaging in breast cancer patients.

Music during image-guided breast biopsy reduces patient anxiety levels.

PURPOSE: Interventions to decrease anxiety associated with image-guided breast biopsy are needed. Music intervention has been shown to be helpful in other outpatient procedural settings but data are limited regarding its effectiveness in the setting of breast biopsy. The purpose of this study was to determine whether listening to self-selected music during image-guided breast biopsy lowers anxiety. MATERIALS AND METHODS: This randomized controlled trial was approved by the institutional review board and was HIPAA-compliant. 157 women between 18 and 75 (mean, 49.7 years) years of age, undergoing stereotactic or ultrasound-guided core biopsy, were enrolled in the study and were prospectively randomized to music or usual care. Patients in the music group listened to music of their choice during the biopsy. All patients completed the State Trait Anxiety Inventory (STAI) before and after the biopsy. Differences in pre-biopsy and post-biopsy anxiety levels were compared between the two groups using the Mann-Whitney U test. RESULTS: Baseline trait anxiety scores in the two groups were similar (34.0 music, 31.5 control, p = .11). Patients in both groups showed lower state anxiety levels after the biopsy (45.6 to 34.3 music, 41.0 to 33.8 control, p < .001 for both). Patients who listened to music showed a greater reduction in anxiety (mean decrease 11.2 music, 7.3 control, p = .03). Post-biopsy anxiety levels were similar to normative values for working women in the same age group. CONCLUSION: Listening to self-selected music reduces anxiety in patients undergoing breast biopsy.

Patient-Reported Breast Density Awareness and Knowledge after Breast Density Legislation Passage.

RATIONALE AND OBJECTIVES: To determine awareness and knowledge of breast density and breast density legislation among women receiving routine mammography following passage of Massachusetts breast density legislation. MATERIALS AND METHODS: A survey assessing breast density awareness and knowledge was administered to all women receiving screening mammography over two separate 1-week periods at an academic medical center following implementation of mandatory breast density notification. Survey questions queried sociodemographic factors, breast density knowledge, legislation awareness, and medical decision-making intent. RESULTS: Of 1000 survey recipients, 338 (33.8%) returned their survey. Most women were surprised (207/338; 61.2%) to receive their breast density notification letter and unaware (302/338; 89.9%) of newly implemented breast density legislation. The majority (185/338; 54.7%) of survey respondents self-reported having dense breasts. Only 61.1% (113/185) of women with dense breasts reported that their personal breast density increased breast cancer risk, while only 60.0% (78/130) of women with non dense breasts reported that their personal breast density did not increase breast cancer risk. Significant differences between women with dense and nondense breasts were observed related to intention to follow-up with a health practitioner (118/185; 63.8% vs. 66/130; 50.8%, p = 0.03) and views on necessity of supplemental screening based on personal breast density (83/185; 45.1% vs. 20/130; 15.4%, p < 0.01). CONCLUSIONS: Despite implementation of state breast density laws since 2009, confusion and misinformation about breast density persists among women receiving mammography screening. Innovative tools that more effectively inform patients, may be required to improve communication and patient understanding about breast density and subsequent breast care management.

Multimodal breast cancer imaging using coregistered dynamic diffuse optical tomography and digital breast tomosynthesis.

Diffuse optical tomography (DOT) is emerging as a noninvasive functional imaging method for breast cancer diagnosis and neoadjuvant chemotherapy monitoring. In particular, the multimodal approach of combining DOT with x-ray digital breast tomosynthesis (DBT) is especially synergistic as DBT prior information can be used to enhance the DOT reconstruction. DOT, in turn, provides a functional information overlay onto the mammographic images, increasing sensitivity and specificity to cancer pathology. We describe a dynamic DOT apparatus designed for tight integration with commercial DBT scanners and providing a fast (up to 1 Hz) image acquisition rate to enable tracking hemodynamic changes induced by the mammographic breast compression. The system integrates 96 continuous-wave and 24 frequency-domain source locations as well as 32 continuous wave and 20 frequency-domain detection locations into low-profile plastic plates that can easily mate to the DBT compression paddle and x-ray detector cover, respectively. We demonstrate system performance using static and dynamic tissue-like phantoms as well as in vivo images acquired from the pool of patients recalled for breast biopsies at the Massachusetts General Hospital Breast Imaging Division.

Intraoperative micro-computed tomography (micro-CT): a novel method for determination of primary tumour dimensions in breast cancer specimens.

OBJECTIVES: Micro-CT is a promising modality to determine breast tumour size in three dimensions in intact lumpectomy specimens. We compared the accuracy of tumour size measurements using specimen micro-CT with measurements using multimodality pre-operative imaging. METHODS: A tabletop micro-CT was used to image breast lumpectomy specimens. The largest tumour dimension on three-dimensional reconstructed micro-CT images of the specimen was compared with the measurements determined by pre-operative mammography, ultrasound and MRI. The largest dimension of pathologic invasive cancer size was used as the gold standard reference to assess the accuracy of imaging assessments. RESULTS: 50 invasive breast cancer specimens in 50 patients had micro-CT imaging. 42 were invasive ductal carcinoma, 6 were invasive lobular carcinoma and 2 were other invasive cancer. Median patient age was 63 years (range 33-82 years). When compared with the largest pathologic tumour dimension, micro-CT measurements had the best correlation coefficient (r = 0.82, p < 0.001) followed by MRI (r = 0.78, p < 0.001), ultrasound (r = 0.61, p < 0.001) and mammography (r = 0.40, p < 0.01). When compared with pre-operative modalities, micro-CT had the best correlation coefficient (r = 0.86, p < 0.001) with MRI, followed by ultrasound (r = 0.60, p < 0.001) and mammography (r = 0.54, p < 0.001). Overall, mammography and ultrasound tended to underestimate the largest tumour dimension, while MRI and micro-CT overestimated the largest tumour dimension more frequently. CONCLUSION: Micro-CT is a potentially useful tool for accurate assessment of tumour dimensions within a lumpectomy specimen. Future studies need to be carried out to see if this technology could have a role in margin assessment. ADVANCES IN KNOWLEDGE: Micro-CT is a promising new technique which could potentially be used for rapid assessment of breast cancer dimensions in an intact lumpectomy specimen in order to guide surgical excision.

How to approach breast lesions in children and adolescents.

UNLABELLED: Assessment of a pediatric breast lesion always starts with clinical evaluation. When imaging of a pediatric breast is indicated, ultrasound is the mainstay. The vast majority of pediatric breast complaints are of benign etiology, therefore the diagnostic/management approach emphasizes "first do no harm". Correlation with age and clinical history helps to direct diagnosis. It is essential to be familiar with the imaging appearance of the normal developing breast at various Tanner stages, in order to diagnose physiologic breast findings and to minimize unnecessary biopsies in young breasts vulnerable to injury. Normal anatomic structures, developmental conditions, benign neoplastic and non-neoplastic lesions are common causes of breast complaints in children. Uncommon benign masses and rarely, secondary more than primary malignancies may present in a pediatric breast. Chest wall masses such as Ewing's sarcoma or rhabdomyosarcoma occur in children and may involve the breast via contiguous growth or locoregional metastasis. In addition, special attention should be given to any breast lesion in a child with risk factors predisposing to breast cancer, such as known extramammary malignancy, genetic mutations, prior mantle irradiation, or strong family history of breast cancer, which usually requires biopsy to exclude the possibility of malignancy. CONCLUSION: The developing breast is vulnerable to injury, and because breast malignancy is uncommon in children, diagnostic and management approach emphasizes "first do no harm". Understanding normal breast development and the spectrum of common and uncommon pediatric breast lesions are key to the correct diagnosis.

To do or not to do: axillary nodal evaluation after ACOSOG Z0011 Trial.

Methods of axillary evaluation in invasive breast cancer continue to evolve. The recent American College of Surgeons Oncology Group Z0011 Trial is a prospective, randomized, multicenter trial that compared the survival and locoregional recurrence rates after complete axillary lymph node dissection (ALND) versus sentinel node biopsy (SNB) alone in women with a positive sentinel node in an effort to avoid the complications associated with ALND. As the results of this trial are implemented clinically, affecting surgical management of axillary metastatic disease, radiologists may need to redefine their role in the preoperative assessment of the axilla. Before the Z0011 trial, breast imagers worked to identify axillary metastases preoperatively, allowing appropriate patients to proceed directly to ALND and avoiding the need for SNB. However, the Z0011 trial concluded that ALND may not be necessary in women with metastatic axillary disease who meet the trial criteria. In the Z0011 trial, after 6 years of median follow-up there was no difference in either locoregional recurrence or survival among the women who underwent SNB alone compared with those who underwent ALND, suggesting that ALND is unnecessary in a subset of women with a positive node at SNB. These results raise questions about how aggressively radiologists should pursue percutaneous sampling of axillary nodes, as some practitioners conclude that, in an otherwise eligible woman, positive results from imaging-guided percutaneous biopsy preclude a Z0011 trial-directed pathway. Debate about the best way to implement the results of the Z0011 trial into daily clinical practice exists. It is important for breast imagers to work closely with breast surgeons to provide the most appropriate treatment course for each patient.

Clinical evaluation of a mobile digital specimen radiography system for intraoperative specimen verification.

OBJECTIVE: Use of mobile digital specimen radiography systems expedites intraoperative verification of excised breast specimens. The purpose of this study was to evaluate the performance of a such a system for verifying targets. MATERIALS AND METHODS: A retrospective review included 100 consecutive pairs of breast specimen radiographs. Specimens were imaged in the operating room with a mobile digital specimen radiography system and then with a conventional digital mammography system in the radiology department. Two expert reviewers independently scored each image for image quality on a 3-point scale and confidence in target visualization on a 5-point scale. A target was considered confidently verified only if both reviewers declared the target to be confidently detected. RESULTS: The 100 specimens contained a total of 174 targets, including 85 clips (49%), 53 calcifications (30%), 35 masses (20%), and one architectural distortion (1%). Although a significantly higher percentage of mobile digital specimen radiographs were considered poor quality by at least one reviewer (25%) compared with conventional digital mammograms (1%), 169 targets (97%), were confidently verified with mobile specimen radiography; 172 targets (98%) were verified with conventional digital mammography. Three faint masses were not confidently verified with mobile specimen radiography, and conventional digital mammography was needed for confirmation. One faint mass and one architectural distortion were not confidently verified with either method. CONCLUSION: Mobile digital specimen radiography allows high diagnostic confidence for verification of target excision in breast specimens across target types, despite lower image quality. Substituting this modality for conventional digital mammography can eliminate delays associated with specimen transport, potentially decreasing surgical duration and increasing operating room throughput.

Micro-computed tomography (Micro-CT): a novel approach for intraoperative breast cancer specimen imaging.

Intraoperative radiographic examination of breast specimens is commonly performed to confirm excision of image-detected breast lesions, but it is not reliable for assessing margin status. A more accurate method of intraoperative breast specimen imaging is needed. Micro-CT provides quantitative imaging parameters, image rotation, and virtual "slicing" of intact breast specimens. We explored the use of micro-CT for assessment of a variety of clinical breast specimens. Specimens were evaluated with a table top micro-CT scanner, Skyscan 1173 (Skyscan, Belgium), with a 40-130 kV, 8 W X-ray source. Skyscan software for 3D image analysis (Dataviewer and CTVox) was employed to review 3D graphics of specimens. Scanning for 7 min and another 7 min for image reconstruction provided the desired resolution for breast specimens. Breast lumpectomy specimens, shaved cavity margins, mastectomy specimens, and axillary lymph nodes were imaged by micro-CT. The micro-CT images could be rotated in all directions and cross sections of internal portions of specimens could be visualized from any angle. This provided information about spatial orientation of masses and calcifications relative to margins in intact lumpectomy specimens. Micro-CT is a potentially useful tool for assessment of breast cancer specimens, allowing real-time analysis of tumor location in breast lumpectomy specimens or shaved cavity margins. Micro-CT may also be useful for assessing sentinel lymph nodes and mastectomy specimens.

Detection of lymph nodes in pelvic malignancies with Computed Tomography and Magnetic Resonance Imaging.

Thirty patients with prostate or bladder cancer underwent CT and MRI for nodal staging. CT detected 189 nodes, and MRI detected 271 nodes. This difference was statistically significant in the external iliac (CT/MRI=73/87 nodes), obturator (CT/MRI=48/75 nodes), and internal iliac (CT/MRI=24/46 nodes) nodal chains. Based on size, the number of nodes detected by CT and MRI were as follows: 1-5 mm, CT/MRI=91/166; 6-10 mm, CT/MRI=91/98; >10 mm, CT/MRI=7/7 nodes. MRI detected significantly more lymph nodes in the size range of 1-5 mm.

Percutaneous renal tumor ablation.

Recent increase in utilization of cross-sectional imaging has resulted in increased detection of early renal cancer. Percutaneous ablation is a relatively new technique for the treatment of renal cancer. This article provides an overview of clinical indications, technique, and results of percutaneous ablation of renal cancer.

Comparison of lymphotropic nanoparticle-enhanced MRI sequences in patients with various primary cancers.

OBJECTIVE: This study was performed to empirically evaluate T2-weighted fast spin-echo, moderately T2*-weighted gradient-refocused echo (GRE), and heavily T2*-weighted GRE sequences to determine which sequence is the most effective for nodal characterization on lymphotropic nanoparticle-enhanced MRI (LNMRI). MATERIALS AND METHODS: The study included 65 patients who had proven primary cancer and were scheduled for either surgical lymph node dissection or imaging-guided lymph node biopsy. All patients underwent LNMRI using T2-weighted fast spin-echo, moderately T2*-weighted GRE, and heavily T2*-weighted GRE sequences. Unequivocal correlation of histopathology and MRI could be made in 140 nodes and only these were included in the analysis. Two blinded reviewers performed qualitative analysis of the nodes. Alternative free-response receiver operating characteristic (ROC) curves with a continuous rating scale were plotted for each sequence for both reviewers and the diagnostic accuracy of fast spin-echo T2-weighted and GRE T2*-weighted images were compared by calculating the area under the curve (A(Z)). A two-tailed Student's t test was performed to test the significance (p < 0.05) of the differences between the ROC curves derived from the three sequences. RESULTS: Irrespective of reviewer experience, T2*-weighted sequences showed better nodal characterization when compared with T2-weighted sequences. For both reviewers, there was a statistically significant difference between the A(Z) for T2- and the two T2*-weighted sequences (p < 0.05). Neither reviewer showed a statistically significant difference between the two T2*-weighted sequences. CONCLUSION: GRE T2*-weighted sequences are superior for nodal characterization on LNMRI to fast spin-echo T2-weighted sequences. Imaging protocols for LNMRI should include fast spin-echo T2-weighted imaging for anatomic localization, but characterization of nodes should be based on their appearance on contrast-enhanced T2*-weighted images. The T2*-weighted images acquired with dual TE values, one of which is intermediate and the other longer, improve nodal characterization.

Lymphotropic nanoparticle enhanced MR imaging (LNMRI) technique for lymph node imaging.

Accurate nodal staging is important in the management of any primary malignancy. The presence of nodal metastases has both therapeutic and prognostic implications. Lymphotropic nanoparticles are a new class of MRI contrast agents, which are promising in detecting minimal metastatic nodal disease particularly in normal sized lymph nodes. This paper discusses the technique and interpretation of lymphotropic nanoparticle enhanced MRI (LNMRI) and reviews the various trials evaluating nodal staging with ferumoxtran-10 enhanced MRI.