Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential

Caspases are a group of proteolytic enzymes involved in the co-ordination of cellular processes, including cellular homeostasis, inflammation and apoptosis. Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation. Furthermore, we found a clear correlation between stromal caspase-4 and -5 expression levels, inflammation and disease activity in ulcerative colitis patients. Deregulated intestinal inflammation in IBD patients is associated with an increased risk of developing CRC. We found robust expression of caspases-4 and -5 within intestinal epithelial cells, exclusively within neoplastic tissue, of colorectal tumours. An examination of adjacent normal, inflamed and tumour tissue from patients with colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is increased in inflamed and dysplastic tissue, while epithelial expression is restricted to neoplastic tissue. In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC

Development of an ensemble CNN model with explainable AI for the classification of gastrointestinal cancer

The implementation of AI assisted cancer detection systems in clinical environments has faced numerous hurdles, mainly because of the restricted explainability of their elemental mechanisms, even though such detection systems have proven to be highly effective. Medical practitioners are skeptical about adopting AI assisted diagnoses as due to the latter's inability to be transparent about decision making processes. In this respect, explainable artificial intelligence (XAI) has emerged to provide explanations for model predictions, thereby overcoming the computational black box problem associated with AI systems. In this particular research, the focal point has been the exploration of the Shapley additive explanations (SHAP) and local interpretable model-agnostic explanations (LIME) approaches which enable model prediction explanations. This study used an ensemble model consisting of three convolutional neural networks(CNN): InceptionV3, InceptionResNetV2 and VGG16, which was based on averaging techniques and by combining their respective predictions. These models were trained on the Kvasir dataset, which consists of pathological findings related to gastrointestinal cancer. An accuracy of 96.89% and F1-scores of 96.877% were attained by our ensemble model. Following the training of the ensemble model, we employed SHAP and LIME to analyze images from the three classes, aiming to provide explanations regarding the deterministic features influencing the model's predictions. The results obtained from this analysis demonstrated a positive and encouraging advancement in the exploration of XAI approaches, specifically in the context of gastrointestinal cancer detection within the healthcare domain

Feasibility of Image Reconstruction from Triple Modality Data of Yttrium-90

The recent implementation of the first clinical triple modality scanner in STIR enables investigation of the possibility of triple modality image reconstruction. Such a tool represents an important step toward the improvement of dosimetry for theranostics, where the exploitation of multi-modality imaging can have an impact on treatment planning and follow-up. To give a demonstration of triple modality image reconstruction we used data from a NEMA phantom that was filled with Yttrium-90 (90Y), which emits Bremsstrahlung photons detectable with SPECT as well as gamma rays that can go through pair production, therefore creating positrons that make PET acquisition possible. The data were acquired with the Mediso AnyScan SPECT/PET/CT. Different ways of including multiple side information using the kernelised expectation maximisation (KEM) and the Hybrid KEM (HKEM) were used and investigated in terms of ROI activity and noise suppression. This work presents an example of application with 90Y but it can be extended to any other radionuclide combination used in Theranostic applications

Improved identification of abdominal aortic aneurysm using the Kernelized Expectation Maximization algorithm

Abdominal aortic aneurysm (AAA) monitoring and risk of rupture is currently assumed to be correlated with the aneurysm diameter. Aneurysm growth, however, has been demonstrated to be unpredictable. Using PET to measure uptake of [18F]-NaF in calcified lesions of the abdominal aorta has been shown to be useful for identifying AAA and to predict its growth. The PET low spatial resolution, however, can affect the accuracy of the diagnosis. Advanced edge-preserving reconstruction algorithms can overcome this issue. The kernel method has been demonstrated to provide noise suppression while retaining emission and edge information. Nevertheless, these findings were obtained using simulations, phantoms and a limited amount of patient data. In this study, the authors aim to investigate the usefulness of the anatomically guided kernelized expectation maximization (KEM) and the hybrid KEM (HKEM) methods and to judge the statistical significance of the related improvements. Sixty-one datasets of patients with AAA and 11 from control patients were reconstructed with ordered subsets expectation maximization (OSEM), HKEM and KEM and the analysis was carried out using the target-to-blood-pool ratio, and a series of statistical tests. The results show that all algorithms have similar diagnostic power, but HKEM and KEM can significantly recover uptake of lesions and improve the accuracy of the diagnosis by up to 22% compared to OSEM. The same improvements are likely to be obtained in clinical applications based on the quantification of small lesions, like for example cancer

Establishing measurement traceability for quantitative SPECT imaging

Background: Single Photon Emission Computed Tomography (SPECT) is increasingly used as a quantitative modality, especially in the context of Molecular Radiotherapy, where the measurements are used as input to absorbed dose calculations for patient-specific dosimetry. Establishing measurement traceability is an essential step in providing confidence in quantitative measurements. This requires an unbroken chain of calibrations where uncertainties must be reported in all stages of calibration and for the final measurement result. Traceability ensures that a measurement result can be related to an underlying standard, allowing harmonisation of data, and facilitating comparison of results between sites. Methods: The process of establishing measurement traceability for quantitative SPECT is demonstrated for the therapeutic radionuclide 177Lu using a common, phantom based, calibration method. Phantoms with activities of 177Lu, measured using a traceably calibrated radionuclide calibrator, were used to perform the calibration. The calibration was validated using 3D-printed anthropomorphic organ phantom inserts mimicking clinically relevant geometries. For all measurements, traceability to primary standards for radioactivity is demonstrated along with an accompanying calibration chain and statement of uncertainty. Results: For all activity measurements the dominant component in the activity uncertainty budget was the uncertainty on the radionuclide calibrator calibration factor, resulting in an average combined standard uncertainty of 1.57%. The resulting uncertainty on the SPECT Image Calibration Factor was 1.6%. An optional additional correction was included in the calibration to provide volume-based partial volume correction (PVC). Measurement traceability was extended for measurands using this additional correction. The activity recovery in the organ phantoms with PVC applied was 96(7)% for both the kidney and spleen. Conclusions: A manufacturer independent methodology for establishing measurement traceability for quantitative SPECT is demonstrated for 177Lu, using a radionuclide calibrator previously calibrated against national standards. The ability to establish measurement traceability for quantitative SPECT using standard clinical equipment, and the limitations of traceability are presented

Hybrid kernelised expectation maximisation for Bremsstrahlung SPECT reconstruction in SIRT with 90Y micro-spheres

BACKGROUND: Selective internal radiation therapy with Yttrium-90 microspheres is an effective therapy for liver cancer and liver metastases. Yttrium-90 is mainly a high-energy beta particle emitter. These beta particles emit Bremsstrahlung radiation during their interaction with tissue making post-therapy imaging of the radioactivity distribution feasible. Nevertheless, image quality and quantification is difficult due to the continuous energy spectrum which makes resolution modelling, attenuation and scatter estimation challenging and therefore the dosimetry quantification is inaccurate. As a consequence a reconstruction algorithm able to improve resolution could be beneficial. METHODS: In this study, the hybrid kernelised expectation maximisation (HKEM) is used to improve resolution and contrast and reduce noise, in addition a modified HKEM called frozen HKEM (FHKEM) is investigated to further reduce noise. The iterative part of the FHKEM kernel was frozen at the 72nd sub-iteration. When using ordered subsets algorithms the data is divided in smaller subsets and the smallest algorithm iterative step is called sub-iteration. A NEMA phantom with spherical inserts was used for the optimisation and validation of the algorithm, and data from 5 patients treated with Selective internal radiation therapy were used as proof of clinical relevance of the method. RESULTS: The results suggest a maximum improvement of 56% for region of interest mean recovery coefficient at fixed coefficient of variation and better identification of the hot volumes in the NEMA phantom. Similar improvements were achieved with patient data, showing 47% mean value improvement over the gold standard used in hospitals. CONCLUSIONS: Such quantitative improvements could facilitate improved dosimetry calculations with SPECT when treating patients with Selective internal radiation therapy, as well as provide a more visible position of the cancerous lesions in the liver

Triple modality image reconstruction of PET data using SPECT, PET, CT information increases lesion uptake in images of patients treated with radioembolization with [Formula: see text] micro-spheres.

PURPOSE: Nuclear medicine imaging modalities like computed tomography (CT), single photon emission CT (SPECT) and positron emission tomography (PET) are employed in the field of theranostics to estimate and plan the dose delivered to tumors and the surrounding tissues and to monitor the effect of the therapy. However, therapeutic radionuclides often provide poor images, which translate to inaccurate treatment planning and inadequate monitoring images. Multimodality information can be exploited in the reconstruction to enhance image quality. Triple modality PET/SPECT/CT scanners are particularly useful in this context due to the easier registration process between images. In this study, we propose to include PET, SPECT and CT information in the reconstruction of PET data. The method is applied to Yttrium-90 ([Formula: see text]Y) data. METHODS: Data from a NEMA phantom filled with [Formula: see text]Y were used for validation. PET, SPECT and CT data from 10 patients treated with Selective Internal Radiation Therapy (SIRT) were used. Different combinations of prior images using the Hybrid kernelized expectation maximization were investigated in terms of VOI activity and noise suppression. RESULTS: Our results show that triple modality PET reconstruction provides significantly higher uptake when compared to the method used as standard in the hospital and OSEM. In particular, using CT-guided SPECT images, as guiding information in the PET reconstruction significantly increases uptake quantification on tumoral lesions. CONCLUSION: This work proposes the first triple modality reconstruction method and demonstrates up to 69% lesion uptake increase over standard methods with SIRT [Formula: see text]Y patient data. Promising results are expected for other radionuclide combination used in theranostic applications using PET and SPECT

The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making

Abstract: Background: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. Results: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5–60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0–25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. Discussion: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes