Institute of Fundamental Technological Research

Yap M., Bill C., Byra M., Ting-yu L., Huahu Y., Galdran A., Yung-Han C., Raphael B., Sven K., Friedrich C., Yu-wen L., Ching-hui Y., Kang L., Qicheng L., Ballester M., Carneiro G., Yi-Jen J., Juinn-Dar H., Pappachan J., Reeves N., Vishnu C., Darren D., Diabetic foot ulcers segmentation challenge report: Benchmark and analysis, Medical Image Analysis, ISSN: 1361-8415, DOI: 10.1016/j.media.2024.103153, Vol.94, No.103153, pp.1-14, 2024

Abstract:
Monitoring the healing progress of diabetic foot ulcers is a challenging process. Accurate segmentation of foot ulcers can help podiatrists to quantitatively measure the size of wound regions to assist prediction of healing status. The main challenge in this field is the lack of publicly available manual delineation, which can be time consuming and laborious. Recently, methods based on deep learning have shown excellent results in automatic segmentation of medical images, however, they require large-scale datasets for training, and there is limited consensus on which methods perform the best. The 2022 Diabetic Foot Ulcers segmentation challenge was held in conjunction with the 2022 International Conference on Medical Image Computing and Computer Assisted Intervention, which sought to address these issues and stimulate progress in this research domain. A training set of 2000 images exhibiting diabetic foot ulcers was released with corresponding segmentation ground truth masks. Of the 72 (approved) requests from 47 countries, 26 teams used this data to develop fully automated systems to predict the true segmentation masks on a test set of 2000 images, with the corresponding ground truth segmentation masks kept private. Predictions from participating teams were scored and ranked according to their average Dice similarity coefficient of the ground truth masks and prediction masks. The winning team achieved a Dice of 0.7287 for diabetic foot ulcer segmentation. This challenge has now entered a live leaderboard stage where it serves as a challenging benchmark for diabetic foot ulcer segmentation.

Keywords:
Deep learning, Diabetic foot ulcers, Segmentation, Convolutional neural networks

Karwat P., Piotrzkowska-Wróblewska H.E., Klimonda Z., Dobruch-Sobczak K., Litniewski J., Monitoring Breast Cancer Response to Neoadjuvant Chemotherapy Using Probability Maps Derived from Quantitative Ultrasound Parametric Images, Ieee Transactions on Biomedical Engineering, ISSN: 0018-9294, DOI: 10.1109/TBME.2024.3383920, Vol.71, No.9, pp.2620-2629, 2024

Abstract:
Objective: Neoadjuvant chemotherapy (NAC) is widely used in the treatment of breast cancer. However, to date, there are no fully reliable, non-invasive methods for monitoring NAC. In this article, we propose a new method for classifying NAC-responsive and unresponsive tumors using quantitative ultrasound. Methods: The study used ultrasound data collected from breast tumors treated with NAC. The proposed method is based on the hypothesis that areas that characterize the effect of therapy particularly well can be found. For this purpose, parametric images of texture features calculated from tumor images were converted into NAC response probability maps, and areas with a probability above 0.5 were used for classification. Results: The results obtained after the third cycle of NAC show that the classification of tumors using the traditional method (AUC = 0.81 - 0.88) can be significantly improved thanks to the proposed new approach (AUC = 0.84–0.94). This improvement is achieved over a wide range of cutoff values (0.2-0.7), and the probability maps obtained from different quantitative parameters correlate well. Conclusion: The results suggest that there are tumor areas that are particularly well suited to assessing response to NAC. Significance: The proposed approach to monitoring the effects of NAC not only leads to a better classification of responses, but also may contribute to a better understanding of the microstructure of neoplastic tumors observed in an ultrasound examination.

Keywords:
breast cancer,neoadjuvant chemotherapy,quantitative ultrasound,treatment monitoring.

Gambin B.J., Kruglenko E., Tymkiewicz R., Litniewski J., Heating efficiency of agarose samples doped with magnetic nanoparticles subjected to ultrasonic and magnetic field, INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER, ISSN: 0017-9310, DOI: 10.1016/j.ijheatmasstransfer.2024.125467, Vol.226, No.125467, pp.1-10, 2024

Abstract:
Recently, magneto-ultrasound heating of tissue in the presence of magnetic nanoparticles (NPs) has been studied due to its high potential for use in oncological hyperthermia. It has been published that a synergistic effect, generation of additional heat caused by magneto-ultrasonic coupling, was observed in a tissue-mimicking material (TMM) enriched with magnetic NPs. The specific absorption rate (SAR) was determined from the temperature rise measurements in a focus of the ultrasound beam. It is important to use precise measurement methods when considering medical applications, for which there are limitations to the power of each field, resulting from the prevention of biological phenomena dangerous to the patient. This study demonstrates that in magneto-ultrasonic heating SAR can be measured much more accurately if the ultrasonic field is almost uniform. Measurements were performed on TMM containing Fe3O4 NPs with a diameter of approximately 8 nm and superparamagnetic properties. Both, the measurement and simulation results showed that the errors resulting from the inaccuracy of placing the temperature probe are smaller than in the case of the focused ultrasound. At the same time, the temperature increase caused by the ultrasonic field is almost linear and the influence of heat convection on the SAR determination is negligible. The measurements showed that magneto-ultrasonic hyperthermia can provide the desired thermal effect at lower ultrasound powers and magnetic fields compared to ultrasonic or magnetic hyperthermia used alone. No synergy effect was recorded.

Keywords:
Magnetic nanoparticle-mediated hyperthermia,Dual-mode ultrasonic-magnetic hyperthermia,Specific absorption rate,Hyperthermia efficiency

Pawłowska A., Ćwierz-Pieńkowska A., Domalik A., Jaguś D., Kasprzak P., Matkowski R., Fura , Nowicki A., Żołek N.S., Curated benchmark dataset for ultrasound based breast lesion analysis, Scientific Data, ISSN: 2052-4463, DOI: 10.1038/s41597-024-02984-z, Vol.11, No.148, pp.1-13, 2024

Abstract:
A new detailed dataset of breast ultrasound scans (BrEaST) containing images of benign and malignant lesions as well as normal tissue examples, is presented. The dataset consists of 256 breast scans collected from 256 patients. Each scan was manually annotated and labeled by a radiologist experienced in breast ultrasound examination. In particular, each tumor was identified in the image using a freehand annotation and labeled according to BIRADS features and lexicon. The histopathological classification of the tumor was also provided for patients who underwent a biopsy.
The BrEaST dataset is the first breast ultrasound dataset containing patient-level labels, image-level annotations, and tumor-level labels with all cases confirmed by follow-up care or core needle biopsy result. To enable research into breast disease detection, tumor segmentation and classification, the BrEaST dataset is made publicly available with the CC-BY 4.0 license.

Olszewski R., Watros K., Mańczak M., Owoc J., Jeziorski K., Brzeziński J., Assessing the response quality and readability of chatbots in cardiovascular health, oncology, and psoriasis: A comparative study, International Journal of Medical Informatics, ISSN: 1386-5056, DOI: 10.1016/j.ijmedinf.2024.105562, Vol.190, No.105562, pp.1-7, 2024

Abstract:
Background: Chatbots using the Large Language Model (LLM) generate human responses to questions from all
categories. Due to staff shortages in healthcare systems, patients waiting for an appointment increasingly use
chatbots to get information about their condition. Given the number of chatbots currently available, assessing the
responses they generate is essential.
Methods: Five chatbots with free access were selected (Gemini, Microsoft Copilot, PiAI, ChatGPT, ChatSpot) and
blinded using letters (A, B, C, D, E). Each chatbot was asked questions about cardiology, oncology, and psoriasis.
Responses were compared to guidelines from the European Society of Cardiology, American Academy of
Dermatology and American Society of Clinical Oncology. All answers were assessed using readability scales
(Flesch Reading Scale, Gunning Fog Scale Level, Flesch-Kincaid Grade Level and Dale-Chall Score). Using a 3-
point Likert scale, two independent medical professionals assessed the compliance of the responses with the
guidelines.
Results: A total of 45 questions were asked of all chatbots. Chatbot C gave the shortest answers, 7.0 (6.0 – 8.0), and Chatbot A the longest 17.5 (13.0 – 24.5). The Flesch Reading Ease Scale ranged from 16.3 (12.2 – 21.9)
(Chatbot D) to 39.8 (29.0 – 50.4) (Chatbot A). Flesch-Kincaid Grade Level ranged from 12.5 (10.6 – 14.6) (Chatbot A) to 15.9 (15.1 – 17.1) (Chatbot D). Gunning Fog Scale Level ranged from 15.77 (Chatbot A) to 19.73 (Chatbot D). Dale-Chall Score ranged from 10.3 (9.3 – 11.3) (Chatbot A) to 11.9 (11.5 – 12.4) (Chatbot D).
Conclusion: This study indicates that chatbots vary in length, quality, and readability. They answer each question
in their own way, based on the data they have pulled from the web. Reliability of the responses generated by
chatbots is high. This suggests that people who want information from a chatbot need to be careful and verify the answers they receive, particularly when they ask about medical and health aspects.

Keywords:
Chatbots,Readability,Cardiovascular health,Oncology

Zaszczyńska A., Gradys A.D., Ziemiecka A., Szewczyk P., Tymkiewicz R., Lewandowska-Szumieł M., Stachewicz U., Sajkiewicz P.Ł., Enhanced Electroactive Phases of Poly(vinylidene Fluoride) Fibers for Tissue Engineering Applications, International Journal of Molecular Sciences, ISSN: 1422-0067, DOI: 10.3390/ijms25094980, Vol.25, No.9, pp.4980-1-25, 2024

Abstract:
Nanofibrous materials generated through electrospinning have gained significant attention in tissue regeneration, particularly in the domain of bone reconstruction. There is high interest in designing a material resembling bone tissue, and many scientists are trying to create materials applicable to bone tissue engineering with piezoelectricity similar to bone. One of the prospective candidates is highly piezoelectric poly(vinylidene fluoride) (PVDF), which was used for fibrous scaffold formation by electrospinning. In this study, we focused on the effect of PVDF molecular weight (180,000 g/mol and 530,000 g/mol) and process parameters, such as the rotational speed of the collector, applied voltage, and solution flow rate on the properties of the final scaffold. Fourier Transform Infrared Spectroscopy allows for determining the effect of molecular weight and processing parameters on the content of the electroactive phases. It can be concluded that the higher molecular weight of the PVDF and higher collector rotational speed increase nanofibers’ diameter, electroactive phase content, and piezoelectric coefficient. Various electrospinning parameters showed changes in electroactive phase content with the maximum at the applied voltage of 22 kV and flow rate of 0.8 mL/h. Moreover, the cytocompatibility of the scaffolds was confirmed in the culture of human adipose-derived stromal cells with known potential for osteogenic differentiation. Based on the results obtained, it can be concluded that PVDF scaffolds may be taken into account as a tool in bone tissue engineering and are worth further investigation.

Keywords:
scaffolds,polymers,piezoelectricity,bone tissue engineering,nanofibers,regenerative medicine

Żyłka A., Dobruch-Sobczak K., Piotrzkowska-Wróblewska H. E., Jędrzejczyk M., Bakuła-Zalewska E., Góralski P., Gałczyński P., Dedecjusz M., The Utility of Contrast-Enhanced Ultrasound (CEUS) in Assessing the Risk of Malignancy in Thyroid Nodules, Cancers, ISSN: 2072-6694, DOI: 10.3390/cancers16101911, Vol.16, No.10, pp.1-23, 2024

Abstract:
Ultrasonography is a basic tool used in the evaluation of thyroid nodules, but there is no single feature of this method which predicts malignancy with statistical significance. The aim of the study is to assess the usefulness of contrast enhanced-ultrasound (CEUS) in the differential diagnosis of thyroid nodules. The highest value of the study results from the multiparameter approach to the evaluation of thyroid lesions in the light of new diagnostics methods and assessment of the unique combinations of both B-mode and CEUS features as predictors of thyroid cancers. Moreover, several qualitative contrast features predicting benign lesions were evaluated. The preliminary results indicate that CEUS is a useful tool in assessing the risk of malignancy of thyroid lesions. The combination of the qualitative enhancement parameters and B-mode sonographic features significantly increases the method’s usefulness. Further studies should be performed to introduce CEUS patterns in the diagnostic algorithm of thyroid nodules.

Keywords:
thyroid cancer, cancer screening, clinical trial, contrast-enhanced ultrasound, thyroid lesion

Kaplińska-Kłosiewicz P.M., Fura Ł., Kujawska T., Andrzejewski K., Kaczyńska K., Strzemecki D., Sulejczak M., Chrapusta S., Macias M., Sulejczak D., Study of Biological Effects Induced in Solid Tumors by Shortened-Duration Thermal Ablation Using High-Intensity Focused Ultrasound, Cancers, ISSN: 2072-6694, DOI: 10.3390/cancers16162846, Vol.16, No.2846, pp.1-23, 2024

Abstract:
The HIFU ablation technique is limited by the long duration of the procedure, which results from the large difference between the size of the HIFU beam’s focus and the tumor size. Ablation of large tumors requires treating them with a sequence of single HIFU beams, with a specific time interval in-between. The aim of this study was to evaluate the biological effects induced in a malignant solid tumor of the rat mammary gland, implanted in adult Wistar rats, during HIFU treatment according to a new ablation plan which allowed researchers to significantly shorten the duration of the procedure. We used a custom, automated, ultrasound imaging-guided HIFU ablation device. Tumors with a 1 mm thickness margin of healthy tissue were subjected to HIFU. Three days later, the animals were sacrificed, and the HIFU-treated tissues were harvested. The biological effects were studied, employing morphological, histological, immunohistochemical, and ultrastructural techniques. Massive cell death, hemorrhages, tissue loss, influx of immune cells, and induction of pro-inflammatory cytokines were observed in the HIFU-treated tumors. No damage to healthy tissues was observed in the area surrounding the safety margin. These results confirmed the efficacy of the proposed shortened duration of the HIFU ablation procedure and its potential for the treatment of solid tumors.

Keywords:
HIFU thermal ablation, breast cancer model, treatment plan, morphology, histology, ultrastructure, immune response, cell death, apoptosis, necrosis

Fura Ł., Tymkiewicz R., Kujawska T., Numerical studies on shortening the duration of HIFU ablation therapy and their experimental validation, Ultrasonics, ISSN: 0041-624X, DOI: 10.1016/j.ultras.2024.107371, Vol.142, No.107371, pp.1-15, 2024

Abstract:
High Intensity Focused Ultrasound (HIFU) is used in clinical practice for thermal ablation of malignant and benign solid tumors located in various organs. One of the reason limiting the wider use of this technology is the long treatment time resulting from i.a. the large difference between the size of the focal volume of the heating beam and the size of the tumor. Therefore, the treatment of large tumors requires scanning their volume with a sequence of single heating beams, the focus of which is moved in the focal plane along a specific trajectory with specific time and distance interval between sonications. To avoid an undesirable increase in the temperature of healthy tissues surrounding the tumor during scanning, the acoustic power and exposure time of each HIFU beam as well as the time intervals between sonications should be selected in such a way as to cover the entire volume of the tumor with necrosis as quickly as possible. This would reduce the costs of treatment. The aim of this study was to quantitatively evaluate the hypothesis that selecting the average acoustic power and exposure time for each individual heating beam, as well as the temporal intervals between sonications, can significantly shorten treatment time. Using 3D numerical simulations, the dependence of the duration of treatment of a tumor with a diameter of 5 mm or 9 mm (requiring multiple exposure to the HIFU beam) on the sonication parameters (acoustic power, exposure time) of each single beam capable of delivering the threshold thermal dose (CEM43 = 240 min) to the treated tissue volume was examined. The treatment duration was determined as the sum of exposure times to individual beams and time intervals between sonications. The tumor was located inside the ex vivo tissue sample at a depth of 12.6 mm. The thickness of the water layer between the HIFU transducer and the tissue was 50 mm. The sonication and scanning parameters selected using the developed algorithm shortened the duration of the ablation procedure by almost 14 times for a 5-mm tumor and 20 times for a 9-mm tumor compared to the duration of the same ablation plan when a HIFU beam was used of a constant acoustic power, constant exposure time (3 s) and constant long time intervals (120 s) between sonications. Results of calculations of the location and size of the necrotic lesion formed were experimentally verified on ex vivo pork loin samples, showing good agreement between them. In this way, it was proven that the proper selection of sonication and scanning parameters for each HIFU beam allows to significantly shorten the time of HIFU therapy.

Keywords:
HIFU ablation planning,HIFU therapy duration shortening,Tissue ex vivo,k-wave model,Experimental verification of therapy accuracy,Numerical simulation

Trots I., Tasinkiewicz J., Nowicki A., Mutually Orthogonal Complementary Golay Coded Sequences: An In-vivo Study, ARCHIVES OF ACOUSTICS, ISSN: 0137-5075, DOI: 10.24425/aoa.2024.148807, Vol.49, No.3, pp.429-437, 2024

Abstract:
Fast and high-quality ultrasound imaging allows to increase the effectiveness of detecting tissue changes at the initial stage of disease. The aim of the study was to assess the quality of ultrasound imaging using mutually
orthogonal, complementary Golay coded sequences (MOCGCS). Two 16-bits MOCGCS sets were implemented in the Verasonics Vantage™ scanner. Echoes from a perfect reflector, a custom-made nylon wire phantom,a tissue-mimicking phantom, and in-vivo scans of abdominal aorta and common carotid artery were recorded.Three parameters of the detected MOCGCS echoes: signal-to-noise ratio (SNR), side-lobe level (SLL), and axial resolution were evaluated and compared to the same parameters of the echoes recorded using standard
complementary Golay sequences (CGS) and a short, one sine cycle pulse. The results revealed that MOCGCS
transmission maintained comparable echo quality metrics (SNR, SLL, and axial resolution) compared to CGS
and short pulses. Notably, both MOCGCS and CGS offered similar SNR improvements (5 dB–9 dB) in compar-ison to the short pulse for wires placed at depths up to 8 cm. Analysis of axial resolution, estimated at the full width at half maximum level, revealed near-identical values for all transmitted signals (0.17 μs for MOCGCS,0.16 μs for CGS, and 0.18 μs for short pulse). MOCGCS implementation in ultrasound imaging offers the po-tential to significantly reduce image reconstruction time while maintaining image quality comparable to CGS sequences. In the experimental study we have shown that MOCGCS offers advantages over conventional CGS by enabling two times faster data acquisition and image reconstruction without compromising image quality.

Keywords:
coded excitation, Golay codes, synthetic aperture

Żyłka A., Dobrych-Sobczak K., Piotrzkowska-Wróblewska H. E., Jędrzejczyk M., Góralski P., Gałczyński J., Zalewska Elwirą B., Dedecjusz M., Ultrasound and cytopathological characteristics of thyroid tumours of uncertain malignant potential — from diagnosis to treatment, Endokrynologia Polska, ISSN: 0423-104X, DOI: 10.5603/ep.98488, Vol.75, No.2, pp.170-178, 2024

Abstract:
Introduction:
The latest World Health Organization (WHO) classification from 2022 distinguishes the division of low-risk thyroid neoplasms such as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), follicular tumour of uncertain malignant potential (FT-UMP), and well-differentiated tumour of uncertain malignant potential (WDT-UMP). The final diagnosis is made postoperatively according to histopathologic results. The aim of the study was the assessment of ultrasonographic and cytopathological features of borderline lesions to predict low-risk tumours preoperatively and plan the optimal treatment for that group of patients.

Material and methods:
A total of 35 patients (30 women; 5 men), aged 20–81 years with a mean age of 49 years, were enrolled in the study. The study evaluated 35 focal lesions of the thyroid gland, classified as low-risk neoplasms according to the WHO 2022 classification: FT-UMP (n = 21), NIFTP (n = 7), and WDT-UMP (n = 7). Ultrasonographic features of nodules including contrast-enhanced ultrasound (CEUS) and elastography were assessed by 2 specialists, and the risk of malignancy was evaluated according to EU-TIRADS-PL classification.

Results:
Of the 35 focal thyroid lesions, most were categorised as low or intermediate risk of malignancy according to EU-TIRADS-PL, with dominant category 3 [n = 13 (37.2%)] and category 4 [n = 15 (42.8%)]. High-risk category 5 was assessed in 7 lesions (20%). In cytopathology nodules were categorised as follows (Bethesda System TBSRTC 2023): Bethesda II (n = 4), Bethesda III (n = 2), Bethesda IV (n = 25), Bethesda V (n = 3), and Bethesda VI (n = 1). In the CEUS study, contrasting patterns dominated compared to the surrounding parenchyma, such as enhancement equal to the parenchyma (66.6%) or intense (28.5%), heterogeneous (61.9%), centripetal (42.8%), or diffuse (57.1%) with fast (33.3%) or compared to parenchyma contrast wash-in (42.8%) and its fast (33.3%) or comparable to thyroid parenchyma wash-out (52.3%).

Conclusions:
The study indicates that lesions with uncertain malignant potential typically present features suggesting low to intermediate risk of malignancy based on EU-TIRADS-PL classification, with dominant cytopathologic Bethesda IV category. However, 20% of lesions were assessed tas EU-TIRADS-PL category 5. Low-risk tumours, including NIFTP, FT-UMP, and WDT-UMP, require careful observation and monitoring post surgical treatment due to their potential for recurrence and metastasis. The preoperatively prediction of borderline tumour may play an important role in proper treatment and follow-up.

Keywords:
thyroid tumour, ultrasound, thyroid cancer, contrast-enhanced-ultrasound