Predicting the Early Response to Neoadjuvant Therapy with Breast MR Morphological, Functional and Relaxometry Features-A Pilot Study.

Aim: To evaluate the role of MR relaxometry and derived proton density analysis in the prediction of early treatment response after two cycles of neoadjuvant therapy (NAT), in patients with breast cancer. Methods: This was a prospective study that included 59 patients with breast cancer, who underwent breast MRI prior (MRI1) and after two cycles of NAT (MRI2). The MRI1 included a sequential acquisition with five different TE's (50, 100, 150, 200 and 250 ms) and a TR of 5000 ms. Post-processing was used to obtain the T2 relaxometry map from the MR acquisition. The tumor was delineated and seven relaxometry and proton density parameters were extracted. Additional histopathology data, T2 features and ADC were included. The response to NAT was reported based on the MRI2 as responders: partial response (>30% decreased size) and complete response (no visible tumor stable disease (SD); and non-responders: stable disease or progression (>20% increased size). Statistics was done using Medcalc software. Results: There were 50 (79.3%) patients with response and 13 (20.7%) non-responders to NAT. Age, histologic type, "in situ" component, tumor grade, estrogen and progesterone receptors, ki67% proliferation index and HER2 status were not associated with NAT response (all p > 0.05). The nodal status (N) 0 was associated with early response, while N2 was associated with non-response (p = 0.005). The tumor (T) and metastatic (M) stage were not statistically significant associated with response (p > 0.05). The margins, size and ADC values were not associated with NAT response (p-value > 0.05). The T2 min relaxometry value was associated with response (p = 0.017); a cut-off value of 53.58 obtained 86% sensitivity (95% CI 73.3−94.2), 69.23 specificity (95% CI 38.6−90.9), with an AUC = 0.715 (p = 0.038). The combined model (T2 min and N stage) achieved an AUC of 0.826 [95% CI: 0.66−0.90, p-value < 0.001]. Conclusions: MR relaxometry may be a useful tool in predicting early treatment response to NAT in breast cancer patients.

Shear-Wave Elastography and Viscosity PLUS for the Assessment of Peripheric Muscles in Healthy Subjects: A Pre- and Post-Contraction Study.

Viscosity is a novel parameter, recently introduced in the use of elastographic techniques, correlating to shear-wave dispersion. The purpose of this study was to provide normal reference viscosity values for the peripheral muscles in healthy volunteers. This prospective study included 38 subjects who underwent US examinations between November 2021 and January 2022. Measurements were taken on the calf and the deltoid muscles in both pre- and post-contraction states. The age range was 21-29 years, with a median of 26 years. The SWE and ViPLUS values in the deltoid muscles were significantly higher than in the soleus muscles in both pre- and post-contraction sets (p = 0.002). There were statistically significant differences between the pre- and post-contraction values for both the SWE and ViPLUS values in the subgroup analysis. The ICC estimates and the 95% confidence intervals were based on a mean rating (k = 2), an absolute agreement, and a two-way random-effects model, demonstrating excellent agreement between the measurements taken by the two examiners.

Radiomic Signatures Derived from Hybrid Contrast-Enhanced Ultrasound Images (CEUS) for the Assessment of Histological Characteristics of Breast Cancer: A Pilot Study.

The purpose of this study was to evaluate the diagnostic performance of radiomic features extracted from standardized hybrid contrast-enhanced ultrasound (CEUS) data for the assessment of hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, tumor grade and Ki-67 in patients with primary breast cancer. METHODS: This prospective study included 72 patients with biopsy-proven breast cancer who underwent CEUS examinations between October 2020 and September 2021. RESULTS: A radiomic analysis found the WavEnHH_s_4 parameter as an independent predictor associated with the HER2+ status with 76.92% sensitivity, and 64.41% specificity and a prediction model that could differentiate between the HER2 entities with 76.92% sensitivity and 84.75% specificity. The RWavEnLH_s-4 parameter was an independent predictor for estrogen receptor (ER) status with 55.93% sensitivity and 84.62% specificity, while a prediction model (RPerc01, RPerc10 and RWavEnLH_s_4) could differentiate between the progesterone receptor (PR) status with 44.74% sensitivity and 88.24% specificity. No texture parameter showed statistically significant results at the univariate analysis when comparing the Nottingham grade and the Ki-67 status. CONCLUSION: Our preliminary data indicate a potential that hybrid CEUS radiomic features allow the discrimination between breast cancers of different receptor and HER2 statuses with high specificity. Hybrid CEUS radiomic features might have the potential to provide a noninvasive, easily accessible and contrast-agent-safe method to assess tumor biology before and during treatment.

Functional Evaluation of Major Salivary Glands Using Viscosity PLUS and 2D Shear-Wave PLUS Elastography Techniques in Healthy Subjects-A Pilot Study.

Biological soft tissues are characterized by viscoelastic properties. The propagation of shear waves within tissues is influenced by both elasticity, which is linked to the shear wave speed, and viscosity, which is linked to the shear wave dispersion. This study aimed to functionally assess the parotid glands (PG) and submandibular glands (SMG) in a group of 40 healthy subjects using the novel Viscosity PLUS (Vi.PLUS) and 2D Shear-Wave Elastography PLUS (2D-SWE.PLUS) techniques. The viscosity and stiffness of PG and SMG were measured before and after gustatory stimulation with a sialagogue agent (commercially available lemon juice) using the new SuperSonic MACH 30 ultrasound system equipped with a curvilinear C6-1X transducer. PG presented a mean basal viscosity and elasticity of 2.10 ± 0.19 Pa.s and 11.32 ± 1.91 kPa, respectively, which significantly increased poststimulation to 2.39 ± 0.17 Pa.s (p < 0.001) and 12.58 ± 1.92 kPa (p < 0.001), respectively. SMG did not present statistically increased values of viscosity and elasticity following stimulation (2.31 ± 015 Pa.s vs. 2.37 ± 0.18 Pa.s, p = 0.086, and 10.40 ± 1.64 kPa vs. 10.90 ± 1.98 kPa, p = 0.074, respectively). Vi.PLUS measurements presented a good positive correlation with 2D-SWE.PLUS values for PG and SMG, before and after stimulation. Gender and BMI were not confounding factors for these two parameters. Vi.PLUS represents an innovative non-invasive imaging technique that, together with 2D-SWE.PLUS proves to be useful in functionally assessing the major salivary glands in healthy subjects.

Comparison of Linear and Convex-Array Transducers in Assessing the Enhancement Characteristics of Suspicious Breast Lesions at Contrast-Enhanced Ultrasound (CEUS).

The purpose of this study was to determine the observer agreement in assessing the enhancement pattern of suspicious breast lesions with contrast-enhanced ultrasound (CEUS) using high and low frequency transducers. Methods: This prospective study included 70 patients with suspicious breast lesions detected at mammography and/or ultrasound and classified according to the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) in 4A, 4B, 4C, or 5, who underwent CEUS examinations between October 2020 and August 2021. Results: Participants' ages ranged from 28 to 83 years (48.5 + 6.36, mean age + SD). We obtained a substantial agreement for the first reader (kappa = 0.614, p < 0.001) and a perfect agreement for the second and third reader (kappa = 1, p < 0.001) between the two transducers for the uptake pattern. A moderate agreement for the second and third reader (kappa = 0.517 and 0.538, respectively, p < 0.001) and only a fair agreement (kappa = 0.320, p < 0.001) in the case of the first reader for the perilesional enhancement was observed. We obtained an excellent inter-observer agreement (Cronbach's Alpha coefficient = 0.960, p < 0.001) for the degree of enhancement, a good inter-observer agreement for the uptake pattern and perilesional enhancement (Cronbach's Alpha coefficient = 0.831 and 0.853, respectively, p < 0.001), and a good and acceptable inter-observer agreement for internal homogeneity, perfusion defects and margins of the lesions (Cronbach's Alpha coefficient = 0.703, 0.703 and 0.792, respectively, p < 0.001) concerning the evaluation of breast lesions with the linear-array transducer. Conclusions: The evaluation of suspicious breast lesions by three experts with high-frequency linear-array transducer and low-frequency convex-array transducer was comparable in terms of uptake pattern and perilesional enhancement. The agreement regarding the evaluation of the degree of enhancement, the internal homogeneity, and the perfusion defects varied between fair and substantial. For all CEUS characteristics, the inter-observer agreement was superior for linear-array transducer, which leads to more a homogeneous and reproducible interpretation.

Associating Automated Breast Ultrasound (ABUS) and Digital Breast Tomosynthesis (DBT) with Full-Field Digital Mammography (FFDM) in Clinical Practice in Cases of Women with Dense Breast Tissue.

The purpose of the present study was to evaluate the value of full-field digital mammography (FFDM) and automated breast ultrasound (ABUS) in the diagnosis of breast cancer compared to FFDM associated with digital breast tomosynthesis (DBT). Methods: This retrospective study included 50 female patients with a denser framework of connective tissue fibers, characteristic of young women who underwent FFDM, DBT, handheld ultrasound (HHUS), and ABUS between January 2017 and October 2018. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and accuracy of FFDM+ABUS were 81.82% (95% CI [48.22-97.72]), 89.74% (95% CI [75.78-97.13]), 69.23% (95% CI [46.05-85.57]), 94.59% (95% CI [83.26-98.40]), and 88% (95% CI [75.69-95.47]), while for FFDM+DBT, the values were as follows: 91.67% (95% CI [61.52-99.79]), 71.79% (95% CI [55.13-85.00]), 50% (95% CI [37.08-62.92]), 96.55% (95% CI [80.93-99.46]), 76.47% (95% CI [62.51-87.21]). We found an almost perfect agreement between the two readers regarding FFDM associated with ABUS, and substantial agreement regarding FFDM+DBT, with a kappa coefficient of 0.896 and 0.8, respectively; p < 0.001. Conclusions: ABUS and DBT are suitable as additional diagnostic imaging techniques to FFDM in women at an intermediate risk of developing breast cancer through the presence of dense breast tissue. In this study, DBT reduced the number of false negative results, while the use of ABUS resulted in an increase in specificity.

Viscosity Plane-wave UltraSound (ViPLUS) in the assessment of parotid and submandibular glands in healthy subjects - preliminary results.

AIMS: Viscosity is an important mechanical property directly linked to the shear wave dispersion within tissues. The purpose of this study was to establish the normal viscosity value of the parotid gland (PG) and submandibular gland (SMG) in a group of healthy subjects, using the novel Viscosity Plane-wave UltraSound (ViPLUS) technique, and to assess its potential dependence on gender and age. MATERIAL AND METHODS: The study group included a total of 49 healthy volunteers (median age 31, 65% females) prospectively examined between February 2021 and March 2021. The viscosity of both PG and SMG was measured using the new Aixplorer MACH 30 ultrasound system (SuperSonic Imagine, Aix-en-Provence, France) equipped with a curvilinear C6-1X transducer. The mean value of three valid measurements was considered (quantified in Pa.s). RESULTS: The mean viscosity value for the PG was 2.13±0.23 Pa.s, significantly lower than the mean viscosity value of the SMG 2.44±0.35 Pa.s (p<0.0001). A negative low correlation between SMG viscosity and age was found (rho=-0.38, p=0.006). Viscosity values of the SMG were significantly lower in the age group between 35-77 years (2.12±0.35 Pa.s) than in the age groups 25-34 years (2.52±0.36 Pa.s), and 20-24 years (2.53±0.24 Pa.s), respectively (p<0.05). Viscosity values of both salivary glands did not differ significantly between gender groups. CONCLUSIONS: Supersonic ViPLUS represents an innovative and useful non-invasive method to assess the viscosity of the parotid and submandibular glands. Age is a potential confounding factor in the evaluation of normal SMG viscosity.

Perineural spread in head and neck malignancies: imaging findings - an updated literature review.

Perineural spread (PNS) represents the tumor's ability to disseminate along nerves. The aim of this article is to review the relevant literature about the PNS in head and neck tumors (HN). The important information for imaging analysis is summarized in a diagnostic flow-chart. The pathogenesis, clinical signs, prognostic importance, and technical considerations for computer tomography and magnetic resonance imaging are briefly discussed. The anatomical pathways of the cranial nerves (CNs) and the main check-points are synthesized. Most commonly affected nerves are the trigeminal and facial, although any of the CNs may be involved. The described imaging features represent important clues for an optimal differential diagnosis. PNS worsens the prognosis and significantly changes the treatment, thus radiologists should be aware of this entity and be able to find it on imaging in the appropriate clinical context.

Role of dynamic contrast enhanced magnetic resonance imaging in the diagnosis and management of vascular lesions of the head and neck.

Vascular anomalies comprise a wide and heterogeneous group of lesions that may be found in all parts of the body, with most of the cases of vascular malformations involving the head and neck region. Ultrasound (US) is the reliable first-line imaging technique to assess flow parameters. However, in some cases, US fails to depict the real extent of the lesions. On the other hand, magnetic resonance imaging (MRI) allows the evaluation of the full extension and anatomic relationship of the vascular anomalies with the neighboring structures and provides hemodynamic characterization using dynamic contrast enhanced MRI (DCE-MRI), avoiding unnecessary invasive catheter-based procedures. DCE-MRI angiography can make a distinction between low and high flow vascular anomalies and it is useful for selecting adequate therapy and appreciating prognosis. The aim of this paper is to review the role of DCE -MRI in the evaluation of flow characteristics and lesion extent in vascular anomalies of the head and neck region.

Differentiating Breast Tumors from Background Parenchymal Enhancement at Contrast-Enhanced Mammography: The Role of Radiomics-A Pilot Reader Study.

BACKGROUND: The purpose of this study was to assess the effectiveness of the radiomic analysis of contrast-enhanced spectral mammography (CESM) in discriminating between breast cancers and background parenchymal enhancement (BPE). METHODS: This retrospective study included 38 patients that underwent CESM examinations for clinical purposes between January 2019-December 2020. A total of 57 malignant breast lesions and 23 CESM examinations with 31 regions of BPE were assessed through radiomic analysis using MaZda software. The parameters that demonstrated to be independent predictors for breast malignancy were exported into the B11 program and a k-nearest neighbor classifier (k-NN) was trained on the initial groups of patients and was tested using a validation group. Histopathology results obtained after surgery were considered the gold standard. RESULTS: Radiomic analysis found WavEnLL_s_2 parameter as an independent predictor for breast malignancies with a sensitivity of 68.42% and a specificity of 83.87%. The prediction model that included CH1D6SumAverg, CN4D6Correlat, Kurtosis, Perc01, Perc10, Skewness, and WavEnLL_s_2 parameters had a sensitivity of 73.68% and a specificity of 80.65%. Higher values were obtained of WavEnLL_s_2 and the prediction model for tumors than for BPEs. The comparison between the ROC curves provided by the WaveEnLL_s_2 and the entire prediction model did not show statistically significant results (p = 0.0943). The k-NN classifier based on the parameter WavEnLL_s_2 had a sensitivity and specificity on training and validating groups of 71.93% and 45.16% vs. 60% and 44.44%, respectively. CONCLUSION: Radiomic analysis has the potential to differentiate CESM between malignant lesions and BPE. Further quantitative insight into parenchymal enhancement patterns should be performed to facilitate the role of BPE in personalized clinical decision-making and risk assessment.

Molecular Pathology and Targeted Therapies for Personalized Management of Central Nervous System Germinoma.

Intracranial germinomas are rare tumours, usually affecting male paediatric patients. They frequently develop in the pineal and suprasellar regions, causing endocrinological disturbances, visual deficits, and increased intracranial pressure. The diagnosis is established on magnetic resonance imaging (MRI), serum and cerebrospinal fluid (CSF) markers, and tumour stereotactic biopsy. Imaging techniques, such as susceptibility-weighted imaging (SWI), T2* (T2-star) gradient echo (GRE) or arterial spin labelling based perfusion-weighted MRI (ASL-PWI) facilitate the diagnosis. Germinomas are highly radiosensitive tumours, with survival rates >90% in the context of chemoradiotherapy. However, patients with resistant disease have limited therapeutic options and poor survival. The aim of this review is to highlight the genetic, epigenetic, and immunologic features, which could provide the basis for targeted therapy. Intracranial germinomas present genetic and epigenetic alterations (chromosomal aberrations, KIT, MAPK and PI3K pathways mutations, DNA hypomethylation, miRNA dysregulation) that may represent targets for therapy. Tyrosine kinase and mTOR inhibitors warrant further investigation in these cases. Immune markers, PD-1 (programmed cell death protein 1) and PD-L1 (programmed death-ligand 1), are expressed in germinomas, representing potential targets for immune checkpoint inhibitors. Resistant cases should benefit from a personalized management: genetic and immunological testing and enrolment in trials evaluating targeted therapies in intracranial germinomas.

Pros and Cons for Automated Breast Ultrasound (ABUS): A Narrative Review.

Automated breast ultrasound (ABUS) is an ultrasound technique that tends to be increasingly used as a supplementary technique in the evaluation of patients with dense glandular breasts. Patients with dense breasts have an increased risk of developing breast cancer compared to patients with fatty breasts. Furthermore, for this group of patients, mammography has a low sensitivity in detecting breast cancers, especially if it is not associated with architectural distortion or calcifications. ABUS is a standardized examination with many advantages in both screening and diagnostic settings: it increases the detection rate of breast cancer, improves the workflow, and reduces the examination time. On the other hand, like any imaging technique, ABUS has disadvantages and even some limitations. Many disadvantages can be diminished by additional attention and training. Disadvantages regarding image acquisition are the inability to assess the axilla, the vascularization, and the elasticity of a lesion, while concerning the interpretation, the disadvantages are the artifacts due to poor positioning, lack of contact, motion or lesion related. This article reviews and discusses the indications, the advantages, and disadvantages of the method and also the sources of error in the ABUS examination.

Inter- and intraobserver reproducibility of Strain and 2D Shear Wave Elastography - a phantom study.

AIMS: To analyse the intra- and interobserver variability of two elastographic methods of quantification available on the same machine, the technical factors that may influence variability as well as the intra- and interobserver variability for the same indices between two different ultrasound machines in an in vitro experimental setting. MATERIAL AND METHODS: Three different types of silicone experimental devices (ED) were conceived for the purpose of this study. Two observers performed repeated measurements on two ultrasound machines. Strain elastography, with strain ratio determination between the ED was performed on both machines. Shear wave ratio was also assessed. The data obtained were used to calculate intra- and interobservervariability. Reproducibility was assessed in relation to the size of the elastographic region of interest (ROI) and to the difference in stiffness between the ED, through the value of the ICCs (Intraclass Correlation Coefficient). RESULTS: Strain ratio had high inter- and intraobserver reproducibility, regardless of the machine used, on a large number of determinations.The choice of a small ROI diameter (5 mm) over a large ROI diameter (15mm) increased reproducibility (ICC = 0.87 vs 0.78, p=0.000). It is observed that, by Shear Wave Elastography, only when analysing structures with a large difference in hardness, significance is obtained in terms of interobserver reproducibility (ICC = 0.75, p=0.000). CONCLUSIONS: On a large number of determinations, both techniques are inter- and intraobserver reproducible. It is preferable to opt for a smaller ROI diameter in order to increase interobserver reproducibility. SWE Ratio provides significant reproducibility only when analysing structureswith large difference in hardness.

Contrast-Enhanced Ultrasonography in the Diagnosis and Treatment Modulation of Breast Cancer.

The aim of this paper is to highlight the role of contrast-enhanced ultrasound in breast cancer in terms of diagnosis, staging and follow-up of the post-treatment response. Contrast-enhanced ultrasound (CEUS) is successfully used to diagnose multiple pathologies and has also clinical relevance in breast cancer. CEUS has high accuracy in differentiating benign from malignant lesions by analyzing the enhancement characteristics and calculating the time-intensity curve's quantitative parameters. It also has a significant role in axillary staging, especially when the lymph nodes are not suspicious on clinical examination and have a normal appearance on gray-scale ultrasound. The most significant clinical impact consists of predicting the response to neoadjuvant chemotherapy, which offers the possibility of adjusting the therapy by dynamically evaluating the patient. CEUS is a high-performance, feasible, non-irradiating, accessible, easy-to-implement imaging method and has proven to be a valuable addition to breast ultrasound.

Pros and cons for breast cancer screening with tomosynthesis - a review of the literature.

Breast cancer screening programs using mammography proved their value in detecting breast cancer at early stages and, consequently, reducing the mortality from this disease. Due to the technological progress, the screening programs have shifted from screen-film mammography to digital mammography and nowadays digital breast tomosynthesis became the focus of breast imaging research. Using tomosynthesis in screening increases cancer detection rates and decreases recall and false-positive rates, thus improving the effectiveness of breast cancer screening programs, with positive consequences on health care costs and on patient psychology. More long-term follow-up data must be collected for assessing absolute sensitivity and specificity of digital breast tomosynthesis, together with efforts for addressing the limitations of the method.

Pectoralis muscle metastases from breast cancer in a young patient detected by automated breast ultrasound.

Metastases to the skeletal muscle from breast cancer represent an unusual and rare condition. We present the case of a 27-year-old female with left breast cancer (IDC NST G3) who underwent neoadjuvant chemotherapy followed by conservativesurgery (sectorectomy and lymphadenectomy) and radiation therapy. Two months after the end of radiotherapy she presented with a 2 mm skin lesion and she was referred for a screening ultrasound. The screening automated breast ultrasound (ABUS) revealed local recurrence and pectoralis metastases, lesions evaluated also by magnetic resonance imaging. The diagnosis was confirmed by the ultrasound-guided biopsy.

Fibroadenomas and breast carcinoma: a possible answer to a frequently asked question. A pictorial essay.

Fibroadenomas (FAs) are the most frequently encountered benign breast lesions in young women and due to the age of the patients, they are usually diagnosed by ultrasound. Although they rarely undergo malignant transformation, the patients remain concerned about the possibility of malignant transformation. The aim of this pictorial essay is to illustrate the appearance of classic and complex fibroadenomas, to discuss the risk factors and to highlight the imaging characteristics that raise the suspicion of malignant transformation. In other words, we try to answer, according to our experience and literature data, to a frequently asked question in daily practice: "Is there any risk thatmy fibroadenoma will become malignant?"

Breast cystic lesions: Not so simple after all? An ultrasonographic tactical approach.

A wide spectrum of breast diseases breast diseases have or exhibit at some point in their natural history a complex cystic aspect. Through the lens of B-mode and Doppler ultrasound with sonoelastographic augmentation, conditions ranging from the utterly benign fibrocystic change to the most intricate encysted or cystically degenerated cancerous lesions, are covered in detail in this review. The aim of this paper is to familiarize the practitioner with the ultrasonographic aspects of complex breast cystic masses and to implement a gradual, strategic approach in the diagnostic algorithm.

Strain Elastography (SE) for liver fibrosis estimation - which elastic score to calculate?

Liver fibrosis scoring by liver biopsy has become a rarity in daily practice mainly because many non-invasive methods with similar accuracy have been developed. Among all ultrasound elastography imaging methods, Strain Elastography (SE) is the most widely available. Although SE is a qualitative and semi-quantitative method, there is reliable applicability for liver fibrosis estimation and multiple ways to transform SE into a quantitative method, in order to obtain a fibrosis score. The aim of this review is to briefly introduce all these methods and to offer support in choosing the best estimation method for liver fibrosis, with SE.

Breast Involvement in Pure Cutaneous Rosai-Dorfman Disease: Ultrasound and Sonoelastography Appearance With a Review of the Literature.

Rosai-Dorfman disease or sinus histiocytosis of the lymph nodes is a rare, idiopathic, and benign disorder. Painless lymphadenopathy is the most frequent systemic presenting symptom and involves the cervical region in up to 90% of the patients. Extranodal involvement is less common and can represent the initial or the only presentation of the disease. We present the ultrasound and sonoelastographic features of a case of extranodal, pure cutaneous Rosai-Dorfman disease involving the breast, in which the breast involvement led to the final diagnosis. We discuss the ultrasound appearance of the disease (on B-mode, Doppler ultrasound, and sonoelastography) with a review of the literature and the different morphological patterns encountered in extranodal and cutaneous involvement.