Tau PET positivity predicts clinically relevant cognitive decline driven by Alzheimer's disease compared to comorbid cases; proof of concept in the ADNI study.

ß-amyloid (Aß) pathology is not always coupled with Alzheimer's disease (AD) relevant cognitive decline. We assessed the accuracy of tau PET to identify Aß(+) individuals who show prospective disease progression. 396 cognitively unimpaired and impaired individuals with baseline Aß and tau PET and a follow-up of ≥ 2 years were selected from the Alzheimer's Disease Neuroimaging Initiative dataset. The participants were dichotomously grouped based on either clinical conversion (i.e., change of diagnosis) or cognitive deterioration (fast (FDs) vs. slow decliners (SDs)) using data-driven clustering of the individual annual rates of cognitive decline. To assess cognitive decline in individuals with isolated Aß(+) or absence of both Aß and tau (T) pathologies, we investigated the prevalence of non-AD comorbidities and FDG PET hypometabolism patterns suggestive of AD. Baseline tau PET uptake was higher in Aß(+)FDs than in Aß(-)FD/SDs and Aß(+)SDs, independently of baseline cognitive status. Baseline tau PET uptake identified MCI Aß(+) Converters and Aß(+)FDs with an area under the curve of 0.85 and 0.87 (composite temporal region of interest) respectively, and was linearly related to the annual rate of cognitive decline in Aß(+) individuals. The T(+) individuals constituted largely a subgroup of those being Aß(+) and those clustered as FDs. The most common biomarker profiles in FDs (n = 70) were Aß(+)T(+) (n = 34, 49%) and Aß(+)T(-) (n = 19, 27%). Baseline Aß load was higher in Aß(+)T(+)FDs (M = 83.03 ± 31.42CL) than in Aß(+)T(-)FDs (M = 63.67 ± 26.75CL) (p-value = 0.038). Depression diagnosis was more prevalent in Aß(+)T(-)FDs compared to Aß(+)T(+)FDs (47% vs. 15%, p-value = 0.021), as were FDG PET hypometabolism pattern not suggestive of AD (86% vs. 50%, p-value = 0.039). Our findings suggest that high tau PET uptake is coupled with both Aß pathology and accelerated cognitive decline. In cases of isolated Aß(+), cognitive decline may be associated with changes within the AD spectrum in a multi-morbidity context, i.e., mixed AD.

Fast three-dimensional image generation for healthy brain aging using diffeomorphic registration.

Predicting brain aging can help in the early detection and prognosis of neurodegenerative diseases. Longitudinal cohorts of healthy subjects scanned through magnetic resonance imaging (MRI) have been essential to understand the structural brain changes due to aging. However, these cohorts suffer from missing data due to logistic issues in the recruitment of subjects. This paper proposes a methodology for filling up missing data in longitudinal cohorts with anatomically plausible images that capture the subject-specific aging process. The proposed methodology is developed within the framework of diffeomorphic registration. First, two novel modules are introduced within Synthmorph, a fast, state-of-the-art deep learning-based diffeomorphic registration method, to simulate the aging process between the first and last available MRI scan for each subject in three-dimensional (3D). The use of image registration also makes the generated images plausible by construction. Second, we used six image similarity measurements to rearrange the generated images to the specific age range. Finally, we estimated the age of every generated image by using the assumption of linear brain decay in healthy subjects. The methodology was evaluated on 2662 T1-weighted MRI scans from 796 healthy participants from 3 different longitudinal cohorts: Alzheimer's Disease Neuroimaging Initiative, Open Access Series of Imaging Studies-3, and Group of Neuropsychological Studies of the Canary Islands (GENIC). In total, we generated 7548 images to simulate the access of a scan per subject every 6 months in these cohorts. We evaluated the quality of the synthetic images using six quantitative measurements and a qualitative assessment by an experienced neuroradiologist with state-of-the-art results. The assumption of linear brain decay was accurate in these cohorts (R2  ∈ [.924, .940]). The experimental results show that the proposed methodology can produce anatomically plausible aging predictions that can be used to enhance longitudinal datasets. Compared to deep learning-based generative methods, diffeomorphic registration is more likely to preserve the anatomy of the different structures of the brain, which makes it more appropriate for its use in clinical applications. The proposed methodology is able to efficiently simulate anatomically plausible 3D MRI scans of brain aging of healthy subjects from two images scanned at two different time points.

CRP as an early indicator for anastomotic leakage after esophagectomy for cancer: a single tertiary gastro-esophageal center study.

PURPOSE: To determine the relationship between postoperative C-reactive protein (CRP) as an early indicator of anastomotic leakage (AL) after esophagectomy for esophageal cancer. METHODS: We reviewed patients diagnosed with esophageal or esophagogastric junctional cancer who underwent esophagectomy between 2006 and 2022 at the Karolinska University Hospital, Stockholm, Sweden. Multivariable logistic regression models estimated relative risk for AL by calculating the odds ratio (OR) with a 95% confidence interval (CI). The cut-off values for CRP were based on the maximum Youden's index using receiver operating characteristic curve analysis. RESULTS: In total, 612 patients were included, with 464 (75.8%) in the non-AL (N-AL) group and 148 (24.2%) in the AL group. Preoperative body mass index and the proportion of patients with the American Society of Anesthesiologists physical status classification 3 were significantly higher in the AL group than in the N-AL group. The median day of AL occurrence was the postoperative day (POD) 8. Trends in CRP levels from POD 2 to 3 and POD 3 to 4 were significantly higher in the AL than in the N-AL group. An increase in CRP of ≥ 4.65% on POD 2 to 3 was an independent risk factor for AL with the highest OR of 3.67 (95% CI 1.66-8.38, p = 0.001) in patients with CRP levels on POD 2 above 211 mg/L. CONCLUSION: Early changes in postoperative CRP levels may help to detect AL early following esophageal cancer surgery.

White matter abnormalities mediate the association between masticatory dysfunction and cognition among older adults.

BACKGROUND: Masticatory parameters, such as reduced number of teeth and posterior contacts, have been shown to be associated with reduced cognitive status. The underlying mechanisms that affect these associations, are however, not well understood. OBJECTIVES: The study aims to investigate the association between masticatory dysfunction and cognition and explore the mediating effect of brain structure. METHODS: In this cross-sectional study, 45 older adults with subjective masticatory dysfunction (mean age 72.3 ± 4.0 years) were included. Mini-Mental State Examination score <25, brain trauma, neurological disease, neurodegenerative disorders, depression or poor Swedish language skills were criteria for exclusion. Cognitive functions (executive function and episodic memory) and masticatory dysfunction defined by functional occluding status (FOS; the number of occluding units and number of remaining teeth) were analysed with partial correlation models. Structural magnetic resonance imaging was performed on 28 feasible participants. Multiple regression analyses were performed to evaluate the predictive value of brain structure and white matter hypointensities (WM-hypo) on cognitive functions. A mediation analysis was applied to assess significant predictor/s of the association between FOS and cognition. RESULTS: Both episodic memory and executive functions were positively correlated with FOS. WM-hypo predicted cognitive status (executive function, p ≤ .01). WM-hypo mediated 66.6% (p = 0.06) of the association between FOS and executive functions. CONCLUSION: Associations between FOS and cognitive functions are reported, where FOS, a potential modifiable risk factor, was related to both episodic memory and executive functions. The mediating effect of WM-hypo on the association between FOS and executive functions highlights the impact of the vascularisation of the brain on the link between mastication and cognition. The present study provides increased knowledge that bridges the gap between masticatory dysfunction and cognition.

The Karolinska NeuroCOVID study protocol: Neurocognitive impairment, biomarkers and advanced imaging in critical care survivors.

BACKGROUND: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health-care systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. METHODS: In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge. RESULTS: To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (~4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. CONCLUSION: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.

Nervous System Involvement in Coronavirus Disease 2019: Results from a Retrospective Consecutive Neuroimaging Cohort.

Background Neurologic complications in coronavirus disease 2019 (COVID-19) have been described, but the understanding of their pathophysiologic causes and neuroanatomical correlates remains limited. Purpose To report on the frequency and type of neuroradiological findings in COVID-19. Materials and Methods In this retrospective study, all consecutive adult hospitalized patients with polymerase chain reaction positivity for severe acute respiratory syndrome coronavirus 2 and who underwent neuroimaging at Karolinska University Hospital between March 2 and May 24, 2020, were included. All examinations were systematically re-evaluated by 12 readers. Summary descriptive statistics were calculated. Results A total of 185 patients with COVID-19 (62 years ± 14 [standard deviation]; 138 men) underwent neuroimaging. In total, 222 brain CT, 47 brain MRI, and seven spinal MRI examinations were performed. Intra-axial susceptibility abnormalities were the most common finding (29 of 39; 74%, 95% CI: 58, 87) in patients who underwent brain MRI, often with an ovoid shape suggestive of microvascular pathology and with a predilection for the corpus callosum (23 of 39; 59%; 95% CI: 42, 74) and juxtacortical areas (14 of 39; 36%; 95% CI: 21, 53). Ischemic and macrohemorrhagic manifestations were also observed, but vascular imaging did not demonstrate overt abnormalities. Dynamic susceptibility contrast perfusion MRI in 19 patients did not reveal consistent asymmetries between hemispheres or regions. Many patients (18 of 41; 44%; 95% CI: 28, 60) had leukoencephalopathy and one patient had a cytotoxic lesion of the corpus callosum. Other findings included olfactory bulb signal abnormalities (seven of 37; 19%), prominent optic nerve subarachnoid spaces (20 of 36; 56%), and enhancement of the parenchyma (three of 20; 15%), leptomeninges (three of 20; 15%), cranial nerves (two of 20; 10%), and spinal nerves (two of four; 50%). At MRI follow-up, regression of leukoencephalopathy and progressive leptomeningeal enhancement was observed in one patient each, respectively, which is suggestive of dynamic processes. Conclusion Patients with coronavirus disease 2019 had a wide spectrum of vascular and inflammatory involvement of both the central and peripheral nervous system. © RSNA, 2020 Online supplemental material is available for this article.

Triple Arterial Phase CT of the Liver with Radiation Dose Equivalent to That of Single Arterial Phase CT: Initial Experience.

Purpose To develop and evaluate a triple arterial phase CT liver protocol with a similar radiation dose to that of standard single arterial phase CT in study subjects suspected of having hepatocellular carcinoma (HCC). Materials and Methods The study consisted of a retrospective part A for protocol development (n = 15) and a prospective part B to evaluate diagnostic accuracy (n = 38). All 53 participants underwent perfusion CT with 50 mL contrast material between August 2013 and September 2014. Group B underwent an additional standard multiphasic liver CT examination with 120 mL of contrast material (range, 70-143 mL). Image sets from triple arterial phase imaging were reconstructed from perfusion CT by fusing images from three dedicated arterial time points. Triple arterial phase CT and standard single arterial phase CT were compared by two readers, who assessed subjective image quality and HCC detection rate. A third reader served as reference reader and assessed objective image quality. The paired Student t test, Wilcoxon signed rank test, jackknife alternative free-response receiver operating characteristic (JAFROC), and JAFROC curve were applied. Results The mean volume CT dose index was 11.6 mGy for triple arterial phase CT and 11.9 mGy for standard single arterial phase CT (P = .73). Triple arterial phase CT showed lower image noise and better contrast-to-noise ratio compared with standard single arterial phase CT (P < .001 and P = .032, respectively); however, there was no significant difference in lesion-to-liver-contrast ratio (P = .31). Subjective image quality was good for both protocols. The detection rate of the 65 HCC lesions was 82% for reader 1 and 83% for reader 2 at triple arterial phase CT and 80% for reader 1 and 77% for reader 2 at standard single arterial phase CT (P = .4). Conclusion Triple arterial phase imaging is feasible at the same radiation dose as that used for standard single arterial phase CT. Triple arterial phase imaging provides equivalent to superior image quality and equal HCC detection rate despite the use of less than half the contrast material dose used at standard single arterial phase CT. © RSNA, 2018.

Convolutional neural networks for the differentiation between benign and malignant renal tumors with a multicenter international computed tomography dataset.

OBJECTIVES: To use convolutional neural networks (CNNs) for the differentiation between benign and malignant renal tumors using contrast-enhanced CT images of a multi-institutional, multi-vendor, and multicenter CT dataset. METHODS: A total of 264 histologically confirmed renal tumors were included, from US and Swedish centers. Images were augmented and divided randomly 70%:30% for algorithm training and testing. Three CNNs (InceptionV3, Inception-ResNetV2, VGG-16) were pretrained with transfer learning and fine-tuned with our dataset to distinguish between malignant and benign tumors. The ensemble consensus decision of the three networks was also recorded. Performance of each network was assessed with receiver operating characteristics (ROC) curves and their area under the curve (AUC-ROC). Saliency maps were created to demonstrate the attention of the highest performing CNN. RESULTS: Inception-ResNetV2 achieved the highest AUC of 0.918 (95% CI 0.873-0.963), whereas VGG-16 achieved an AUC of 0.813 (95% CI 0.752-0.874). InceptionV3 and ensemble achieved the same performance with an AUC of 0.894 (95% CI 0.844-0.943). Saliency maps indicated that Inception-ResNetV2 decisions are based on the characteristics of the tumor while in most tumors considering the characteristics of the interface between the tumor and the surrounding renal parenchyma. CONCLUSION: Deep learning based on a diverse multicenter international dataset can enable accurate differentiation between benign and malignant renal tumors. CRITICAL RELEVANCE STATEMENT: Convolutional neural networks trained on a diverse CT dataset can accurately differentiate between benign and malignant renal tumors. KEY POINTS: • Differentiation between benign and malignant tumors based on CT is extremely challenging. • Inception-ResNetV2 trained on a diverse dataset achieved excellent differentiation between tumor types. • Deep learning can be used to distinguish between benign and malignant renal tumors.

Acquisition Duration Optimization Using Visual Grading Regression in [68Ga]FAPI-46 PET Imaging of Oncologic Patients.

Fibroblast activation protein is a promising target for oncologic molecular imaging with radiolabeled fibroblast activation protein inhibitors (FAPI) in a large variety of cancers. However, there are yet no published recommendations on how to set up an optimal imaging protocol for FAPI PET/CT. It is important to optimize the acquisition duration and strive toward an acquisition that is sufficiently short while simultaneously providing sufficient image quality to ensure a reliable diagnosis. The aim of this study was to evaluate the feasibility of reducing the acquisition duration of [68Ga]FAPI-46 imaging while maintaining satisfactory image quality, with certainty that the radiologist's ability to make a clinical diagnosis would not be affected. Methods: [68Ga]FAPI-46 PET/CT imaging was performed on 10 patients scheduled for surgical resection of suspected pancreatic cancer, 60 min after administration of 3.6 ± 0.2 MBq/kg. The acquisition time was 4 min/bed position, and the raw PET data were statistically truncated and reconstructed to represent images with an acquisition duration of 1, 2, and 3 min/bed position, additional to the reference images of 4 min/bed position. Four image quality criteria that focused on the ability to distinguish specific anatomic details, as well as perceived image noise and overall image quality, were scored on a 4-point Likert scale and analyzed with mixed-effects ordinal logistic regression. Results: A trend toward increasing image quality scores with increasing acquisition duration was observed for all criteria. For the overall image quality, there was no significant difference between 3 and 4 min/bed position, whereas 1 and 2 min/bed position were rated significantly (P < 0.05) lower than 4 min/bed position. For the other criteria, all images with a reduced acquisition duration were rated significantly inferior to images obtained at 4 min/bed position. Conclusion: The acquisition duration can be reduced from 4 to 3 min/bed position while maintaining satisfactory image quality. Reducing the acquisition duration to 2 min/bed position or lower is not recommended since it results in inferior-quality images so noisy that clinical interpretation is significantly disrupted.

Prediction of Anastomotic Leakage in Esophageal Cancer Surgery: A Multimodal Machine Learning Model Integrating Imaging and Clinical Data.

RATIONALE AND OBJECTIVES: Surgery in combination with chemo/radiotherapy is the standard treatment for locally advanced esophageal cancer. Even after the introduction of minimally invasive techniques, esophagectomy carries significant morbidity and mortality. One of the most common and feared complications of esophagectomy is anastomotic leakage (AL). Our work aimed to develop a multimodal machine-learning model combining CT-derived and clinical data for predicting AL following esophagectomy for esophageal cancer. MATERIAL AND METHODS: A total of 471 patients were prospectively included (Jan 2010-Dec 2022). Preoperative computed tomography (CT) was used to evaluate celia trunk stenosis and vessel calcification. Clinical variables, including demographics, disease stage, operation details, postoperative CRP, and stage, were combined with CT data to build a model for AL prediction. Data was split into 80%:20% for training and testing, and an XGBoost model was developed with 10-fold cross-validation and early stopping. ROC curves and respective areas under the curve (AUC), sensitivity, specificity, PPV, NPV, and F1-scores were calculated. RESULTS: A total of 117 patients (24.8%) exhibited post-operative AL. The XGboost model achieved an AUC of 79.2% (95%CI 69%-89.4%) with a specificity of 77.46%, a sensitivity of 65.22%, PPV of 48.39%, NPV of 87.3%, and F1-score of 56%. Shapley Additive exPlanation analysis showed the effect of individual variables on the result of the model. Decision curve analysis showed that the model was particularly beneficial for threshold probabilities between 15% and 48%. CONCLUSION: A clinically relevant multimodal model can predict AL, which is especially valuable in cases with low clinical probability of AL.

[ 18 F]-PSMA-1007 PET imaging optimization and inter-rater reliability - a comparison of three different reconstructions read by four radiologists.

OBJECTIVES: To increase understanding of optimal imaging parameters [ 18 F]PSMA-1007 when imaging patients with prostate cancer and to determine interrater agreement using [ 18 F]PSMA-1007. METHODS: In this observational study, four independent physicians read reconstruction sets using bedtimes of 1, 2 and 3 minutes of patients undergoing [ 18 F]PSMA-1007. positron emission topography. Clear and equivocal lesions and their locations were recorded. Image noise was rated on a four-point scale. Lesion counts were compared using inter-class correlation whereas noise ratings were compared using generalized estimating equations. Repeated cases were used to assess intra-rater agreement. RESULTS: Sixty reconstruction sets of 16 consecutively examined participants were included. Participants had a mean age of 71.5 years, six of them were examined prior to any treatment, three had a history of radiotherapy and seven of prostatectomy. Median Gleason score of primary tumors was 7. Imaging was performed after a mean of 132 min using a mean 3.95 MBq/Kg body weight of [ 18 F] PSMA-1007. Neither the total number of lesions per location nor the proportion of equivocal lesions varied consistently between bedtimes. Inter-rater reliability scores varied depending on location from 0.40 to 1.0 and were similar for all bedtimes. Intra-rater reliability varied between 0.70 and 0.76 for the three different bedtimes. Noise ratings were significantly lower for 1 minute than 3 minutes per bed. CONCLUSION: In the setting of [ 18 F]PSMA-1007 PET CT, 1, 2 and 3 minutes per bed produce similar results unlikely to affect clinical interpretation. Image noise ratings favor 2 and 3 minutes per bed.

Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [68Ga]Ga-ABY-025: Results from a Pilot Study.

Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [68Ga]Ga-ABY-025 for visualization of HER2-low mBC. Methods: A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [68Ga]Ga-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of [68Ga]Ga-ABY-025. The SUVmax was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome-the safety and feasibility of HER2 PET in patients with HER2-low mBC, measured the occurrence of possible procedure-related adverse events. Results: Ten patients with HER2-low mBC underwent [68Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [68Ga]Ga-ABY-025-avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025-avid lesions, the HER2-low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUVmax and 1 in a liver metastasis with a high SUVmax but a "cold" core. Conclusion: The visualization of HER2-low mBC with [68Ga]Ga-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in [68Ga]Ga-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.

Machine Learning Integrating 99mTc Sestamibi SPECT/CT and Radiomics Data Achieves Optimal Characterization of Renal Oncocytic Tumors.

The increasing evidence of oncocytic renal tumors positive in 99mTc Sestamibi Single Photon Emission Tomography/Computed Tomography (SPECT/CT) examination calls for the development of diagnostic tools to differentiate these tumors from more aggressive forms. This study combined radiomics analysis with the uptake of 99mTc Sestamibi on SPECT/CT to differentiate benign renal oncocytic neoplasms from renal cell carcinoma. A total of 57 renal tumors were prospectively collected. Histopathological analysis and radiomics data extraction were performed. XGBoost classifiers were trained using the radiomics features alone and combined with the results from the visual evaluation of 99mTc Sestamibi SPECT/CT examination. The combined SPECT/radiomics model achieved higher accuracy (95%) with an area under the curve (AUC) of 98.3% (95% CI 93.7-100%) than the radiomics-only model (71.67%) with an AUC of 75% (95% CI 49.7-100%) and visual evaluation of 99mTc Sestamibi SPECT/CT alone (90.8%) with an AUC of 90.8% (95%CI 82.5-99.1%). The positive predictive values of SPECT/radiomics, radiomics-only, and 99mTc Sestamibi SPECT/CT-only models were 100%, 85.71%, and 85%, respectively, whereas the negative predictive values were 85.71%, 55.56%, and 94.6%, respectively. Feature importance analysis revealed that 99mTc Sestamibi uptake was the most influential attribute in the combined model. This study highlights the potential of combining radiomics analysis with 99mTc Sestamibi SPECT/CT to improve the preoperative characterization of benign renal oncocytic neoplasms. The proposed SPECT/radiomics classifier outperformed the visual evaluation of 99mTc Sestamibii SPECT/CT and the radiomics-only model, demonstrating that the integration of 99mTc Sestamibi SPECT/CT and radiomics data provides improved diagnostic performance, with minimal false positive and false negative results.

Radiomics Analysis for Multiple Myeloma: A Systematic Review with Radiomics Quality Scoring.

Multiple myeloma (MM) is one of the most common hematological malignancies affecting the bone marrow. Radiomics analysis has been employed in the literature in an attempt to evaluate the bone marrow of MM patients. This manuscript aimed to systematically review radiomics research on MM while employing a radiomics quality score (RQS) to accurately assess research quality in the field. A systematic search was performed on Web of Science, PubMed, and Scopus. The selected manuscripts were evaluated (data extraction and RQS scoring) by three independent readers (R1, R2, and R3) with experience in radiomics analysis. A total of 23 studies with 2682 patients were included, and the median RQS was 10 for R1 (IQR 5.5-12) and R3 (IQR 8.3-12) and 11 (IQR 7.5-12.5) for R2. RQS was not significantly correlated with any of the assessed bibliometric data (impact factor, quartile, year of publication, and imaging modality) (p > 0.05). Our results demonstrated the low quality of published radiomics research in MM, similarly to other fields of radiomics research, highlighting the need to tighten publication standards.

A pilot radiometabolomics integration study for the characterization of renal oncocytic neoplasia.

Differentiating benign renal oncocytic tumors and malignant renal cell carcinoma (RCC) on imaging and histopathology is a critical problem that presents an everyday clinical challenge. This manuscript aims to demonstrate a novel methodology integrating metabolomics with radiomics features (RF) to differentiate between benign oncocytic neoplasia and malignant renal tumors. For this purpose, thirty-three renal tumors (14 renal oncocytic tumors and 19 RCC) were prospectively collected and histopathologically characterised. Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) was used to extract metabolomics data, while RF were extracted from CT scans of the same tumors. Statistical integration was used to generate multilevel network communities of -omics features. Metabolites and RF critical for the differentiation between the two groups (delta centrality > 0.1) were used for pathway enrichment analysis and machine learning classifier (XGboost) development. Receiver operating characteristics (ROC) curves and areas under the curve (AUC) were used to assess classifier performance. Radiometabolomics analysis demonstrated differential network node configuration between benign and malignant renal tumors. Fourteen nodes (6 RF and 8 metabolites) were crucial in distinguishing between the two groups. The combined radiometabolomics model achieved an AUC of 86.4%, whereas metabolomics-only and radiomics-only classifiers achieved AUC of 72.7% and 68.2%, respectively. Analysis of significant metabolite nodes identified three distinct tumour clusters (malignant, benign, and mixed) and differentially enriched metabolic pathways. In conclusion, radiometabolomics integration has been presented as an approach to evaluate disease entities. In our case study, the method identified RF and metabolites important in differentiating between benign oncocytic neoplasia and malignant renal tumors, highlighting pathways differentially expressed between the two groups. Key metabolites and RF identified by radiometabolomics can be used to improve the identification and differentiation between renal neoplasms.

Current status of contemporary diagnostic radiotracers in the management of breast cancer: first steps toward theranostic applications.

BACKGROUND: Expanding therapeutic possibilities have improved disease-related prospects for breast cancer patients. Pathological analysis on a tumor biopsy is the current reference standard biomarker used to select for treatment with targeted anticancer drugs. This method has, however, several limitations, related to intra- and intertumoral as well as spatial heterogeneity in receptor expression as well as the need to perform invasive procedures that are not always technically feasible. MAIN BODY: In this narrative review, we focus on the current role of molecular imaging with contemporary radiotracers for positron emission tomography (PET) in breast cancer. We provide an overview of diagnostic radiotracers that represent treatment targets, such as programmed death ligand 1, human epidermal growth factor receptor 2, polyadenosine diphosphate-ribose polymerase and estrogen receptor, and discuss developments in therapeutic radionuclides for breast cancer management. CONCLUSION: Imaging of treatment targets with PET tracers may provide a more reliable precision medicine tool to find the right treatment for the right patient at the right time. In addition to visualization of the target of treatment, theranostic trials with alpha- or beta-emitting isotopes provide a future treatment option for patients with metastatic breast cancer.

[HER2-low breast cancer - A new entity that could expand possibilities of getting treatment]. / HER2-låg bröstcancer ny entitet ­ ökar behandlingsmöjligheterna.

Breast cancer is the most common form of cancer among women in Sweden. Several decades ago it was recognized that the Human epidermal growth factor receptor 2 (HER2) is involved in a critical growth system for breast cancer cells. Overexpression of HER2 (immunohistochemistry [IHC] 2+/3+, in situ hybridization [ISH] positive) is present in 15 percent of all breast cancers. HER2-low breast cancer has been discovered as a separate entity; the most commonly used definition so far is IHC 1+/2+ and ISH negative, but general consensus is still lacking. Clinical studies with the HER2 antibody drug conjugate trastuzumab deruxtecan (Enhertu) have shown impressive antitumor activity among women with advanced HER2-low breast cancer and this is expected to become part of routine treatment in the near future. Research is needed to establish refined ways to define HER2-low breast cancer, and a possible role lies in new imaging methods such as HER2 positron emission tomography (PET) with a [68Ga]Ga-ABY-025 tracer.

Role of Radiology in the Preoperative Detection of Arterial Calcification and Celiac Trunk Stenosis and Its Association with Anastomotic Leakage Post Esophagectomy, an Up-to-Date Review of the Literature.

Surgical resection of the esophagus remains a critical component of the multimodal treatment of esophageal cancer. Anastomotic leakage (AL) is the most significant complication following esophagectomy, in terms of clinical implications. Identifying risk factors for AL is important for modifying patient management and improving surgical outcomes. This review aims to examine the role of radiological risk factors for AL after esophagectomy, and in particular, arterial calcification and celiac trunk stenosis. Eligible publications prior to 25 August 2021 were retrieved from Medline and Google Scholar using a predefined search algorithm. A total of 68 publications were identified, of which 9 original studies remained for in-depth analysis. The majority of these studies found correlations between calcifications in the aorta, celiac trunk, and right post-celiac arteries and AL following esophagectomy. Some studies suggest celiac trunk stenosis as a more appropriate surrogate. Our up-to-date review highlights the need for automated quantification of aortic calcifications, as well as the degree of celiac trunk stenosis in preoperative computed tomography in patients undergoing esophagectomy, to obtain robust and reproducible measurements that can be used for a definite correlation.

99mTc-Sestamibi SPECT/CT and histopathological features of oncocytic renal neoplasia.

BACKGROUND: 99mTc-Sestamibi Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) contributes to the non-invasive differentiation of renal oncocytoma (RO) from renal cell carcinoma (RCC) by characterising renal tumours as Sestamibi positive or Sestamibi negative regarding their 99mTc-Sestamibi uptake compared to the non-tumoral renal parenchyma. PURPOSE: To determine whether 99mTc- Sestamibi uptake in renal tumour and the non-tumoral renal parenchyma measured using Standard Uptake Value (SUV) SPECT, has a beneficial role in differentiating RO from RCC. MATERIAL AND METHODS: Fifty-seven renal tumours from 52 patients were evaluated. In addition to visual evaluation of 99mTc-Sestamibi uptake, SUVmax measurements were performed in the renal tumour and the ipsilateral non-tumoral renal parenchyma. Analysis of the area under the receiver operating characteristic curve identified an optimal cut-off value for detecting RO, based on the relative ratio of 99mTc- Sestamibi uptake. RESULTS: Semiquantitative evaluation of 99mTc-Sestamibi uptake did not improve the performance of 99mTc- Sestamibi SPECT/CT in detecting RO. 99mTc- Sestamibi SPECT/CT identifies a group of mostly indolent Sestamibi-positive tumours with low malignant potential containing RO, Low-Grade Oncocytic Tumours, Hybrid Oncocytic Tumours, and a subset of chromophobe RCCs. CONCLUSION: The imaging limitations for accurate differentiation of Sestamibi-positive renal tumours mirror the recognised diagnostic complexities of the histopathologic evaluation of oncocytic neoplasia. Patients with Sestamibi-positive renal tumours could be better suited for biopsy and follow-up, according to the current active surveillance protocols.

Multimodal perioperative assessment of liver function and volume in patients undergoing hepatectomy for colorectal liver metastasis: a comparison of the indocyanine green retention test, 99mTc mebrofenin hepatobiliary scintigraphy and gadoxetic acid enhanced MRI.

OBJECTIVES: To compare the dynamic changes in future liver remnant (FLR) function and volume after hepatectomy and to evaluate the associations between three modalities in assessment of liver function. METHODS: Liver function and volume were quantified pre-operatively, at post-operative day (POD) 7 and POD 28 in 10 patients with colorectal liver metastases undergoing hemihepatectomy using the indocyanine green retention (ICG) test, hepatobiliary scintigraphy (HBS) and gadoxetic acid-enhanced MRI. The 99mTc mebrofenin uptake rate in the FLR was applied as a reference of liver function. MRI-derived parameters including liver-to-muscle ratio (LMR), liver-to-spleen ratio (LSR) and hepatocellular uptake index (HUI) were used for liver function assessment. Spearman's correlation analysis was used to evaluate the associations. RESULTS: Increase in liver function ranged from 13 to 152% (median 92%) and in volume from 37 to 134% (median 79%). There was no significant discrepancy in increase between FLR function and volume during the first month following hepatectomy. LMR showed a significant correlation to ICG test (r = -0.66, p < 0.05) while LSR had an association with standardized FLR function obtained by HBS (r = -0.71, p < 0.05). During the first week after hepatectomy, pre-operative HUI and LMR showed the strongest correlation to the FLR growth in function and volume respectively (p < 0.05). CONCLUSION: The observed growth in FLR volume is closely related to the functional increase within 1 month after hepatectomy. Gadoxetic acid-enhanced MRI might substitute HBS for regional liver function assessment and provide an imaging tool for liver growth prediction. ADVANCES IN KNOWLEDGE: Liver function growth was parallel with liver volume increase during the perioperative period. Liver function assessment with gadoxetic acid-enhanced MRI was comparable with that of HBS indicating that gadoxetic acid-enhanced MRI could substitute HBS for regional liver function evaluation.