Diffusion-weighted imaging in addition to contrast-enhanced MRI in identifying complete response in HER2-positive breast cancer.

OBJECTIVES: The aim of this study is to investigate the added value of diffusion-weighted imaging (DWI) to dynamic-contrast enhanced (DCE)-MRI to identify a pathological complete response (pCR) in patients with HER2-positive breast cancer and radiological complete response (rCR). MATERIALS AND METHODS: This is a single-center observational study of 102 patients with stage I-III HER2-positive breast cancer and real-world documented rCR on DCE-MRI. Patients were treated between 2015 and 2019. Both 1.5 T/3.0 T single-shot diffusion-weighted echo-planar sequence were used. Post neoadjuvant systemic treatment (NST) diffusion-weighted images were reviewed by two readers for visual evaluation and ADCmean. Discordant cases were resolved in a consensus meeting. pCR of the breast (ypT0/is) was used to calculate the negative predictive value (NPV). Breast pCR-percentages were tested with Fisher's exact test. ADCmean and ∆ADCmean(%) for patients with and without pCR were compared using a Mann-Whitney U-test. RESULTS: The NPV for DWI added to DCE is 86% compared to 87% for DCE alone in hormone receptor (HR)-/HER2-positive and 67% compared to 64% in HR-positive/HER2-positive breast cancer. Twenty-seven of 39 non-rCR DWI cases were false positives. In HR-negative/HER2-positive breast cancer the NPV for DCE MRI differs between MRI field strength (1.5 T: 50% vs. 3 T: 81% [p = 0.02]). ADCmean at baseline, post-NST, and ∆ADCmean were similar between patients with and without pCR. CONCLUSION: DWI has no clinically relevant effect on the NPV of DCE alone to identify a pCR in early HER2-positive breast cancer. The added value of DWI in HR-positive/HER2-positive breast cancer should be further investigated taken MRI field strength into account. CLINICAL RELEVANCE STATEMENT: The residual signal on DWI after neoadjuvant systemic therapy in cases with early HER2-positive breast cancer and no residual pathologic enhancement on DCE-MRI breast should not (yet) be considered in assessing a complete radiologic response. KEY POINTS: Radiologic complete response is associated with a pathologic complete response (pCR) in HER2+ breast cancer but further improvement is warranted. No relevant increase in negative predictive value was observed when DWI was added to DCE. Residual signal on DW-images without pathologic enhancement on DCE-MRI, does not indicate a lower chance of pCR.

Breast DWI Analyzed Before and After Gadolinium Contrast Administration-An Intrapatient Analysis on 1.5 T and 3.0 T.

OBJECTIVES: Diffusion-weighted magnetic resonance imaging (MRI) is gaining popularity as an addition to standard dynamic contrast-enhanced breast MRI. Although adding diffusion-weighted imaging (DWI) to the standard protocol design would require increased scanning-time, implementation during the contrast-enhanced phase could offer a multiparametric MRI protocol without any additional scanning time. However, gadolinium within a region of interest (ROI) might affect assessments of DWI. This study aims to determine if acquiring DWI postcontrast, incorporated in an abbreviated MRI protocol, would statistically significantly affect lesion classification. In addition, the effect of postcontrast DWI on breast parenchyma was studied. MATERIALS AND METHODS: Screening or preoperative MRIs (1.5 T/3 T) were included for this study. Diffusion-weighted imaging was acquired with single-shot spin echo-echo planar imaging before and at approximately 2 minutes after gadoterate meglumine injection. Apparent diffusion coefficients (ADCs) based on 2-dimensional ROIs of fibroglandular tissue, as well as benign and malignant lesions at 1.5 T/3.0 T, were compared with a Wilcoxon signed rank test. Diffusivity levels were compared between precontrast and postcontrast DWI with weighted κ. An overall P ≤ 0.05 was considered statistically significant. RESULTS: No significant changes were observed in ADC mean after contrast administration in 21 patients with 37 ROI of healthy fibroglandular tissue and in the 93 patients with 93 (malignant and benign) lesions. This effect remained after stratification on B 0 . In 18% of all lesions, a diffusion level shift was observed, with an overall weighted κ of 0.75. CONCLUSIONS: This study supports incorporating DWI at 2 minutes postcontrast when ADC is calculated based on b150-b800 with 15 mL 0.5 M gadoterate meglumine in an abbreviated multiparametric MRI protocol without requiring extra scan time.

Predicting breast cancer types on and beyond molecular level in a multi-modal fashion.

Accurately determining the molecular subtypes of breast cancer is important for the prognosis of breast cancer patients and can guide treatment selection. In this study, we develop a deep learning-based model for predicting the molecular subtypes of breast cancer directly from the diagnostic mammography and ultrasound images. Multi-modal deep learning with intra- and inter-modality attention modules (MDL-IIA) is proposed to extract important relations between mammography and ultrasound for this task. MDL-IIA leads to the best diagnostic performance compared to other cohort models in predicting 4-category molecular subtypes with Matthews correlation coefficient (MCC) of 0.837 (95% confidence interval [CI]: 0.803, 0.870). The MDL-IIA model can also discriminate between Luminal and Non-Luminal disease with an area under the receiver operating characteristic curve of 0.929 (95% CI: 0.903, 0.951). These results significantly outperform clinicians' predictions based on radiographic imaging. Beyond molecular-level test, based on gene-level ground truth, our method can bypass the inherent uncertainty from immunohistochemistry test. This work thus provides a noninvasive method to predict the molecular subtypes of breast cancer, potentially guiding treatment selection for breast cancer patients and providing decision support for clinicians.

Optical coherence tomography accurately identifies patients with penile (pre) malignant lesions: A single center prospective study.

INTRODUCTION: Currently, (multiple) biopsies are taken to obtain histopathological diagnosis of suspicious lesions of the penile skin. Optical coherence tomography (OCT) provides noninvasive in vivo images from which epidermal layer thickness and attenuation coefficient (µoct) can be quantified. We hypothesize that qualitative (image assessment) and quantitative (epidermal layer thickness and attenuation coefficient, µoct) analysis of penile skin with OCT is possible and may differentiate benign penile tissue from (pre) malignant penile tissue. MATERIALS AND METHODS: Optical coherence tomography-imaging was performed prior to punch biopsy in 18 consecutive patients with a suspicious lesion at the outpatient clinic of the NKI-AVL. Qualitative analysis consisted of visual assessment of clear layers and a visible lower border of the lesions, quantitative analysis comprised of determination of the epidermal layer thickness and µoct. Results were grouped according to histopathology reports. RESULTS: Qualitative analysis showed a statistically significant difference (P = 0.047) between benign and (pre) malignant lesions. Quantitative analysis showed that epidermal layer thickness and attenuation coefficient was significantly different between benign and (pre) malignant tissue, respectively, P = 0.001 and P < 0.001. CONCLUSION: In this preliminary study, qualitative and quantitative analysis of OCT-images of suspicious penile lesions shows differences between benign lesions and (pre) malignant lesions. These results encourage further research in a larger study population.

Learning curve and interobserver variance in quantification of the optical coherence tomography attenuation coefficient.

The learning curve and interobserver variance of attenuation coefficient (µOCT ) determination from optical coherence tomography (OCT) images were quantified. The µOCT of normal and diseased vulvar tissues was determined at five time points by three novice students and three OCT experts who reached consensus for reference. Students received feedback between time points. Eventually, variance in µOCT was smaller in images of diseased tissue than in images of normal vulvar tissue. The difference between the consensus and student µOCT values was larger for smaller values of µOCT . We conclude that routine µOCT determination for tissue classification does not require extensive training.

The value of optical coherence tomography in determining surgical margins in squamous cell carcinoma of the vulva: a single-center prospective study.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) is treated with wide local excision. The challenge is to remove as much skin as necessary to prevent recurrence, but meanwhile preserve genital skin to diminish morbidity. Optical coherence tomography (OCT) is a noninvasive imaging tool that produces cross-sectional images. Optical coherence tomography could be helpful in determining appropriate surgical margins during excision of VSCC. OBJECTIVE: This study aimed to assess the value of OCT in determining appropriate surgical margins in patients operated for VSCC. We hypothesize that benign tissue will differ qualitatively (presence of clear epidermal layers) and quantitatively (epidermal layer thickness and attenuation coefficient) from (pre)malignant tissue. MATERIALS AND METHODS: In 18 patients with a pretreatment biopsy of VSCC, before excision, areas within the center (tumor), at the margin (skin next to the center), and in normal vulvar skin outside the area of resection were imaged by OCT. Optical coherence tomography data were assessed on the presence of a clear epidermal layer, thickness of the epidermal layer, and values of µOCT. Results were grouped according to histopathological report in a benign group and a (pre)malignant group. RESULTS: A clear epidermal layer was observed in all OCT images of benign tissue and only in 6 of 23 premalignant lesions (P < 0.001). The epidermal layer thickness as well as the µOCT was significantly smaller for benign vulvar tissue than for (pre)malignant tissue (0.29 vs 1.03 mm, and 2.4 vs 4.1 mm(-1), respectively; P < 0.001). The diagnostic accuracy of OCT, as calculated by receiver operating characteristic curve analysis, showed at defined thresholds a sensitivity of 100% and specificity of 80% when considering layer thickness, and a sensitivity of 100% and specificity of 70% when considering the attenuation coefficient. CONCLUSIONS: We show that qualitative and quantitative OCT imaging can distinguish between benign and (pre)malignant vulvar tissue, enabling appropriate surgical margin detection with noninvasive in vivo OCT imaging.

Optical coherence tomography in vulvar intraepithelial neoplasia.

Vulvar squamous cell carcinoma (VSCC) is a gynecological cancer with an incidence of two to three per 100,000 women. VSCC arises from vulvar intraepithelial neoplasia (VIN), which is diagnosed through painful punch biopsy. In this study, optical coherence tomography (OCT) is used to differentiate between normal and VIN tissue. We hypothesize that (a) epidermal layer thickness measured in OCT images is different in normal tissue and VIN, and (b) quantitative analysis of the attenuation coefficient (µoct) extracted from OCT data differentiates VIN from normal vulvar tissue. Twenty lesions from 16 patients are imaged with OCT. Directly after data acquisition, a biopsy is performed. Epidermal thickness is measured and values of µoct are extracted from 200 OCT scans of normal and VIN tissue. For both methods, statistical analysis is performed using Paired Mann-Whitney-test. Correlation between the two methods is tested using a Spearman-correlation test. Both epidermal layer thickness as well as the µoct are different between normal vulvar tissue and VIN lesions (p < 0.0001). Moreover, no correlation is found between the epidermal layer thickness and µoct. This study demonstrates that both the epidermal thickness and the attenuation coefficient of vulvar epithelial tissue containing VIN are different from that of normal vulvar tissue.

Shoulder dislocation in a very-low-birth-weight infant: case report and review of the literature.

Shoulder dislocation in a preterm infant is very rare. We report a case of a preterm infant, with gestational age of 25 2/7 weeks and birth weight of 910 g, with anterior shoulder dislocation after breech delivery. The infant was successfully treated with closed reduction. In general, long-term outcome of shoulder dislocation in these infants is good. However, prompt recognition and treatment of the dislocated shoulder are essential to maintain normal shoulder girdle function and to prevent functional disability.

Plasma ADMA concentrations at birth and mechanical ventilation in preterm infants: a prospective pilot study.

RATIONALE: Nitric oxide (NO) produced in the lung is an important mediator of normal lung development, vascular smooth muscle relaxation, and ventilation perfusion matching. NO is synthesized from arginine by the action of NO-synthase (NOS). Asymmetric dimethylarginine (ADMA), an endogenous derivate of arginine, inhibits NOS and is thereby a determinant of NO synthesis. We compared ADMA and arginine levels in preterm infants requiring mechanical ventilation with preterm infants who did not require mechanical ventilation and determined the relation between ADMA and the length of mechanical ventilation in these infants. METHODS: Thirty preterm infants, mean (SD) gestational age 29.3 (1.7) weeks and birth weight 1,340 (350) gram, of the Neonatal Intensive Care Unit of the VU University Medical Center were included. ADMA and arginine were measured in umbilical cord blood and the length of mechanical ventilation (days) was registered. RESULTS: Gestational age and birth weight were significantly smaller in infants requiring mechanical ventilation, but were not significantly correlated with plasma ADMA concentration after birth. Plasma ADMA concentrations were significantly higher in infants who required mechanical ventilation than in infants who did not require mechanical ventilation (1.53 +/- 0.23 and 1.37 +/- 0.14 micromol/L, respectively; P = 0.036). ADMA concentration was significantly related to length of mechanical ventilation (B = 3.4; 95% CI: 1.1-5.6; P = 0.006), also after adjustment for gestational age (B = 2.3; 95% CI: 0.4-4.2; P = 0.024). CONCLUSIONS: Preterm infants who require mechanical ventilation have increased ADMA levels compared to non-ventilated preterm infants. ADMA levels at birth are related to the length of mechanical ventilation. An increased ADMA concentration could reduce NO synthesis, which could lead to insufficient gas exchange and, consequently, a longer period of mechanical ventilation.