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IEEE Journal of Translational... 2024Pulmonary cavity lesion is one of the commonly seen lesions in lung caused by a variety of malignant and non-malignant diseases. Diagnosis of a cavity lesion is commonly...
OBJECTIVE
Pulmonary cavity lesion is one of the commonly seen lesions in lung caused by a variety of malignant and non-malignant diseases. Diagnosis of a cavity lesion is commonly based on accurate recognition of the typical morphological characteristics. A deep learning-based model to automatically detect, segment, and quantify the region of cavity lesion on CT scans has potential in clinical diagnosis, monitoring, and treatment efficacy assessment.
METHODS
A weakly-supervised deep learning-based method named CSA2-ResNet was proposed to quantitatively characterize cavity lesions in this paper. The lung parenchyma was firstly segmented using a pretrained 2D segmentation model, and then the output with or without cavity lesions was fed into the developed deep neural network containing hybrid attention modules. Next, the visualized lesion was generated from the activation region of the classification network using gradient-weighted class activation mapping, and image processing was applied for post-processing to obtain the expected segmentation results of cavity lesions. Finally, the automatic characteristic measurement of cavity lesions (e.g., area and thickness) was developed and verified.
RESULTS
the proposed weakly-supervised segmentation method achieved an accuracy, precision, specificity, recall, and F1-score of 98.48%, 96.80%, 97.20%, 100%, and 98.36%, respectively. There is a significant improvement (P < 0.05) compared to other methods. Quantitative characterization of morphology also obtained good analysis effects.
CONCLUSIONS
The proposed easily-trained and high-performance deep learning model provides a fast and effective way for the diagnosis and dynamic monitoring of pulmonary cavity lesions in clinic. Clinical and Translational Impact Statement: This model used artificial intelligence to achieve the detection and quantitative analysis of pulmonary cavity lesions in CT scans. The morphological features revealed in experiments can be utilized as potential indicators for diagnosis and dynamic monitoring of patients with cavity lesions.
Topics: Humans; Tomography, X-Ray Computed; Deep Learning; Lung; Radiographic Image Interpretation, Computer-Assisted; Lung Diseases; Lung Neoplasms; Neural Networks, Computer; Supervised Machine Learning; Algorithms
PubMed: 38899144
DOI: 10.1109/JTEHM.2024.3399261 -
JTCVS Techniques Jun 2024Accurate intraoperative diagnosis of spread through air spaces (STAS), a known poor prognostic factor in lung cancer, is crucial for guiding surgical decision-making...
OBJECTIVE
Accurate intraoperative diagnosis of spread through air spaces (STAS), a known poor prognostic factor in lung cancer, is crucial for guiding surgical decision-making during sublobar resections. This study aimed to evaluate the diagnostic sensitivity of STAS using frozen section (FS) slides prepared with the cryo-embedding medium inflation technique.
METHODS
In this prospective study at Shinshu University Hospital, 99 patients undergoing lung resection for tumors <3 cm in size were included, a total of 114 lesions. FS slides were prepared with injecting diluted cryo-embedding medium into the lung parenchyma of resected specimens. The diagnostic performance of these FS slides for STAS detection was evaluated by comparing FS-STAS results with the gold-standard STAS status.
RESULTS
The incidence of STAS, determined by the gold standard, was 43 (38%) of 114 lesions, including 31 (37%) of 84 primary lung cancers and 12 (40%) of 30 metastatic lung tumors. The sensitivity, specificity, positive and negative predictive values, and accuracy of FS slides for STAS detection were 81%, 89%, 81%, 89%, and 86%, respectively. Specifically, in primary lung cancers, these values were 90%, 89%, 82%, 94%, and 89%, respectively. Regarding metastatic lung tumors, the corresponding values were 58%, 89%, 78%, 76%, and 77%, respectively.
CONCLUSIONS
Our adapted cryo-embedding medium inflation method has demonstrated enhanced sensitivity in detecting STAS on FS slides, providing results similar to the gold-standard STAS detection. Compared with historical benchmarks, this technique could show excellent performance and be readily incorporated into clinical practice without requiring additional resources beyond those used for standard FS analysis.
PubMed: 38899076
DOI: 10.1016/j.xjtc.2024.02.014 -
Human Brain Mapping Jun 2024Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS)...
Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1- and T2-weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject-specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal-appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety-nine relapsing-remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty-five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = -0.30, -0.29, -0.33 respectively and r = -.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.
Topics: Humans; Female; Male; Adult; Middle Aged; Brain; Multiple Sclerosis; Diffusion Magnetic Resonance Imaging; Water; Cognitive Dysfunction; Parenchymal Tissue; White Matter; Gray Matter; Processing Speed
PubMed: 38895882
DOI: 10.1002/hbm.26761 -
BioRxiv : the Preprint Server For... Jun 2024Multiple system atrophy (MSA) is rare, fast progressing, and fatal synucleinopathy with alpha-synuclein (α-syn) inclusions located within oligodendroglia called glial...
Multiple system atrophy (MSA) is rare, fast progressing, and fatal synucleinopathy with alpha-synuclein (α-syn) inclusions located within oligodendroglia called glial cytoplasmic inclusions (GCI). Along with GCI pathology there is severe demyelination, neurodegeneration, and neuroinflammation. In post-mortem tissue, there is significant infiltration of CD8+ T cells into the brain parenchyma, however their role in disease progression is unknown. To determine the role of CD8+ T cells, a modified AAV, Olig001-SYN, was used to selectively overexpress α-syn in oligodendrocytes modeling MSA in mice. Four weeks post transduction, we observed significant CD8+ T cell infiltration into the striatum of Olig001-SYN transduced mice recapitulating the CD8+ T cell infiltration observed in post-mortem tissue. To understand the role of CD8+ T cells, a CD8 knockout mice were transduced with Olig001-SYN. Six months post transduction into a mouse lacking CD8+ T cells, demyelination and neurodegeneration were unchanged. Four weeks post transduction, neuroinflammation and demyelination were enhanced in CD8 knockout mice compared to wild type controls. Applying unbiased spectral flow cytometry, CD103+, CD69+, CD44+, CXCR6+, CD8+ T cells were identified when α-syn was present in oligodendrocytes, suggesting the presence of tissue resident memory CD8+ T (Trm) cells during MSA disease progression. This study indicates that CD8+ T cells are not critical in driving MSA pathology but are needed to modulate the neuroinflammation and demyelination response.
PubMed: 38895456
DOI: 10.1101/2024.06.02.597035 -
Cureus May 2024Paget's disease of the bone (PDB) is a benign osteodystrophy of the elderly characterized by excessive remodeling of bone tissue, mainly in the pelvis, femur, and skull....
Paget's disease of the bone (PDB) is a benign osteodystrophy of the elderly characterized by excessive remodeling of bone tissue, mainly in the pelvis, femur, and skull. Its neurological manifestations are numerous and affect both the central and peripheral nervous systems. As headaches are often reported, epileptic seizures remain exceptional. We report the case of a 75-year-old female patient with a history of chronic worsening headache who was admitted to the emergency department for the first episode of a seizure. Brain imaging revealed heterogeneous bone thickening and circumscribed skull osteoporosis. Bone scintigraphy showed pagetoid lesions restricted to the skull and face. Alkaline phosphatases increased. The rest of the biological work-up and the cerebrospinal fluid study ruled out other metabolic causes or central nervous system infections. The patient was treated with bisphosphonates and anti-convulsive treatment. The evolution was satisfactory, with progressive improvement in headache and seizure control, even several months after discontinuation of anti-seizure medication. Our case report highlights the importance of exploring chronic headaches in the elderly, not only in search of lesions of the cerebral parenchyma but also of the structures containing them, in this case, the skull.
PubMed: 38894759
DOI: 10.7759/cureus.60588 -
Journal of Cellular and Molecular... Jun 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by intense deposition of fat globules in the hepatic parenchyma that could potentially...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by intense deposition of fat globules in the hepatic parenchyma that could potentially progress to liver cirrhosis and hepatocellular carcinoma. Here, we evaluated a rat model to study the molecular pathogenesis of the spectrum of MASLD and to screen therapeutic agents. SHRSP5/Dmcr rats were fed a high-fat and cholesterol (HFC) diet for a period of 12 weeks and evaluated for the development of steatosis (MASLD), steatohepatitis, fibrosis and cirrhosis. A group of animals were sacrificed at the end of the 4th, 6th, 8th and 12th weeks from the beginning of the experiment, along with the control rats that received normal diet. Blood and liver samples were collected for biochemical and histopathological evaluations. Immunohistochemical staining was performed for α-SMA and Collagen Type I. Histopathological examinations demonstrated steatosis at the 4th week, steatohepatitis with progressive fibrosis at the 6th week, advanced fibrosis with bridging at the 8th week and cirrhosis at the 12th week. Biochemical markers and staining for α-SMA and Collagen Type I demonstrated the progression of steatosis to steatohepatitis, hepatic fibrosis and liver cirrhosis in a stepwise manner. Control animals fed a normal diet did not show any biochemical or histopathological alterations. The results of the present study clearly demonstrated that the HFC diet-induced model of steatosis, steatohepatitis, hepatic fibrosis and cirrhosis is a feasible, quick and appropriate animal model to study the molecular pathogenesis of the spectrum of MASLD and to screen potent therapeutic agents.
Topics: Animals; Liver Cirrhosis; Rats; Diet, High-Fat; Fatty Liver; Male; Liver; Disease Models, Animal; Collagen Type I; Actins
PubMed: 38894579
DOI: 10.1111/jcmm.18491 -
Diagnostics (Basel, Switzerland) May 2024The clinical use of photon-counting CT (PCCT) allows for the generation of virtual non-contrast (VNC) series from contrast-enhanced images. In routine clinical practice,...
The clinical use of photon-counting CT (PCCT) allows for the generation of virtual non-contrast (VNC) series from contrast-enhanced images. In routine clinical practice, specific issues such as ruling out acute bleeding require non-contrast images. The aim of this study is to evaluate the use of PCCT-derived VNC reconstructions in abdominal imaging. PCCT scans of 17 patients including early arterial, portal venous and native sequences were enrolled. VNC reconstructions have been calculated. In every sequence and VNC reconstruction, 10 ROIs were measured (portal vein, descending aorta, inferior vena cava, liver parenchyma, spleen parenchyma, erector spinae muscle, subcutaneous adipose tissue, first lumbar vertebral body, air, and psoas muscle) and density values were compared. The VNC reconstructions show significant changes in density compared to the contrast-enhanced images. However, there were no significant differences present between the true non-contrast (TNC) and any VNC reconstructions in the observed organs and vessels. Significant differences ( < 0.05) between the measured mean density values in the TNC versus VNC reconstructions were found in fat and bone tissue. The PCCT-derived VNC reconstructions seemed to be comparable to the TNC images, despite some deviations shown in the adipose tissue and bone structures. However, the further benefits in terms of specific clinical issues need to be evaluated.
PubMed: 38893656
DOI: 10.3390/diagnostics14111130 -
Molecules (Basel, Switzerland) Jun 2024Kostel. is a species of mangrove used in traditional Ayurvedic medicine for treating inflammatory conditions. The present study aims to establish monographic botanical...
Kostel. is a species of mangrove used in traditional Ayurvedic medicine for treating inflammatory conditions. The present study aims to establish monographic botanical and chemical quality criteria for leaf and bark as herbal substances and to evaluate their in vitro antioxidant potential. Macroscopic and microscopic qualitative and quantitative analyses, chemical LC-UV/DAD-ESI/MS profiling, and the quantification of key chemical classes were performed. Antioxidant activity was evaluated by DPPH and FRAP assays. Macroscopically, the leaf is asymmetrical with an emarginated apex and cuneate base. Microscopically, it shows features such as two-layered adaxial palisade parenchyma, vascular bundles surrounded by 3-6 layers of sclerenchyma, prismatic calcium oxalate crystals (5.89 ± 1.32 μm) along the fibers, paracytic stomata only on the abaxial epidermis (stomatal index-20.15), and non-glandular trichomes only on petiolules. The microscopic features of the bark include a broad cortex with large lignified sclereids, prismatic calcium oxalate crystals (8.24 ± 1.57 μm), and secondary phloem with distinct 2-5 seriated medullary rays without crystals. Chemical profile analysis revealed that phenolic derivatives, mainly condensed tannins and flavonoids, are the main classes identified. A total of 22 marker compounds were tentatively identified in both plant parts. The major compounds identified in the leaf were quercetin-3--glucoside and taxifolin pentoside and in the bark were B-type dimeric proanthocyanidins and taxifolin 3--rhamnoside. The total phenolics content was higher in the leaf (1521 ± 4.71 mg GAE/g dry weight), while the total flavonoids and condensed tannins content were higher in the bark (82 ± 0.58 mg CE/g and 1021 ± 5.51 mg CCE/g dry weight, respectively). A total of 70% of the hydroethanolic extracts of leaf and bark showed higher antioxidant activity than the ascorbic acid and concentration-dependent scavenging activity in the DPPH assay (IC 23.95 ± 0.93 and 23.63 ± 1.37 µg/mL, respectively). A positive and statistically significant ( < 0.05) correlation between the phenol content and antioxidant activity was found. The results obtained will provide important clues for the quality control criteria of leaf and bark, as well as for the knowledge of their pharmacological potential as possible anti-inflammatory agents with antioxidant activity.
Topics: Plant Bark; Plant Leaves; Antioxidants; Plant Extracts; Plants, Medicinal; Flavonoids; Phytochemicals; Herbal Medicine; Phenols; Proanthocyanidins
PubMed: 38893505
DOI: 10.3390/molecules29112629 -
International Journal of Molecular... May 2024Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis...
Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24-72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUV) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUV compared to controls ( = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET's potential as a non-invasive imaging biomarker for early-stage ALF.
Topics: Animals; Liver Failure, Acute; Acetaminophen; Male; Mice; Mice, Inbred C57BL; Receptors, GABA; Positron-Emission Tomography; Liver; Positron Emission Tomography Computed Tomography; Fluorine Radioisotopes; Radiopharmaceuticals; Disease Models, Animal; Carbazoles
PubMed: 38892130
DOI: 10.3390/ijms25115942 -
Cells May 2024Pulmonary fibrosis is a chronic, progressive, irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive... (Review)
Review
Pulmonary fibrosis is a chronic, progressive, irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (ECM) due to the aberrant activation of myofibroblasts in the alveolar environment. Transforming growth factor beta (TGF-β) signaling is a crucial driver of fibrogenesis because it promotes excessive ECM deposition, thereby leading to scar formation and lung damage. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in ECM deposition and wound repair. TGF-β transcriptionally regulates CTHRC1 in response to tissue injury and controls the wound healing response through functional activity. CTHRC1 may also play an essential role in re-establishing and maintaining tissue homeostasis after wound closure by modulating both the TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 regulates tissue remodeling and homeostasis. However, deregulated CTHRC1 expression in pathogenic fibroblasts has recently emerged as a hallmark of fibrosis in multiple organs and tissues. This review highlights recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, systemic sclerosis, and post-COVID-19 lung fibrosis. Notably, CTHRC1 expression is responsive to antifibrotic drugs that target the TGF-β pathway, such as pirfenidone and bexotegrast, indicating its potential as a biomarker of treatment success. These findings suggest that CTHRC1 may present new opportunities for diagnosing and treating patients with lung fibrosis.
Topics: Humans; Fibroblasts; Extracellular Matrix Proteins; Pulmonary Fibrosis; Animals; Transforming Growth Factor beta; Extracellular Matrix; Idiopathic Pulmonary Fibrosis
PubMed: 38891078
DOI: 10.3390/cells13110946