Umbilical catheters are used in the care of critically ill neonates for intravenous treatment. It is generally considered a safe procedure, although complications can occur. Of these, catheter ...breakage and intravenous migration are rare but potentially life-threatening events. Due to the low frequency of which these events occur, obtaining detailed descriptions of removal techniques can pose a challenge. Here, we describe a case of a broken umbilical vein catheter and the surgical retrieval of the retained fragment. We also present a thorough literature search of cases of broken umbilical catheters and the method by which they were removed.
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•Hyperpolarized 13C-pyruvate MRS and FDG-PET was compared in canine cancer patients.•Lactate generation and FDG uptake correlated for a certain cancer type only.•The relation between ...lactate generation and FDG uptake depended on cancer type.•HyperPET estimates of glycolysis may allow for improved metabolic phenotyping.
13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare hyperpolarized 1-13Cpyruvate MRS with simultaneous 18F-2-fluoro-2-deoxy-d-glucose (FDG) PET in a cross-sectional study of canine cancer patients.
Canine cancer patients underwent integrated PET/MRI using a clinical whole-body system. Hyperpolarized 1-13Cpyruvate was obtained using dissolution-DNP. 18F-FDG PET, dynamic 13C MRS, 13C MRS Imaging (MRSI) and anatomical 1H MRI was acquired from 17 patients. Apparent pyruvate-to-lactate rate constants were estimated from dynamic 13C MRS. 18F-FDG Standard Uptake Values and maximum 1-13Clactate-to-total-13C ratios were obtained from tumor regions of interest. Following inspection of data, patients were grouped according to main cancer type and linear regression between measures of lactate generation and 18F-FDG uptake were tested within groups. Between groups, the same measures were tested for group differences.
The main cancer types of the 17 patients were sarcoma (n = 11), carcinoma (n = 5) and mastocytoma (n = 1). Significant correlations between pyruvate-to-lactate rate constants and 18F-FDG uptake were found for sarcoma patients, whereas no significant correlations appeared for carcinoma patients. The sarcoma patients showed a non-significant trend towards lower 18F-FDG uptake and higher lactate generation than carcinoma patients. However, the ratio of lactate generation to 18F-FDG uptake was found to be significantly higher in sarcoma as compared to carcinoma. The results were found both when lactate generation was estimated as an apparent pyruvate-to-lactate rate constant from dynamic 13C MRS and as an 1-13Clactate to total 13C ratio from 13C MRSI.
A comparison of hyperpolarized 1-13Cpyruvate MRS with simultaneous 18F-FDG PET indicate that lactate generation and 18F-FDG uptake in cancers can be related and that their relation depend on cancer type. This finding could be important for the interpretation and eventual clinical implementation of hyperpolarized 13C. In addition, the differences between the two modalities may allow for better metabolic phenotyping performing hybrid imaging in the form of hyperPET.
PurposeThe diffusion‐weighted SPLICE (split acquisition of fast spin‐echo signals) sequence employs split‐echo rapid acquisition with relaxation enhancement (RARE) readout to provide images almost ...free of geometric distortions. However, due to the varying T2$$ {}_2 $$‐weighting during k‐space traversal, SPLICE suffers from blurring. This work extends a method for controlling the spatial point spread function (PSF) while optimizing the signal‐to‐noise ratio (SNR) achieved by adjusting the flip angles in the refocusing pulse train of SPLICE.MethodsAn algorithm based on extended phase graph (EPG) simulations optimizes the flip angles by maximizing SNR for a flexibly chosen predefined target PSF that describes the desired k‐space density weighting and spatial resolution. An optimized flip angle scheme and a corresponding post‐processing correction filter which together achieve the target PSF was tested by healthy subject brain imaging using a clinical 1.5 T scanner.ResultsBrain images showed a clear and consistent improvement over those obtained with a standard constant flip angle scheme. SNR was increased and apparent diffusion coefficient estimates were more accurate. For a modified Hann k‐space weighting example, considerable benefits resulted from acquisition weighting by flip angle control.ConclusionThe presented flexible method for optimizing SPLICE flip angle schemes offers improved MR image quality of geometrically accurate diffusion‐weighted images that makes the sequence a strong candidate for radiotherapy planning or stereotactic surgery.
PD-1/PD-ligand-axis immunotherapy-mediated activation of T-cells for cancer cell elimination is a promising treatment of nonsmall cell lung cancer (NSCLC). However, the effect of immunotherapy on ...intracellular signaling pathways in cancer cells still needs further delineation. Repulsive Guidance Molecule b (RGMb), a regulator of Bone Morphogenetic Proteins (BMPs) signaling, interacts with the PD-ligand, PD-L2, at cancer cell membranes. Accordingly, a clarification of the functions of RGMb and its relation to PD-L2 might provide insight into NSCLC cell signaling responses to PD-1/PD-ligand-axis immunotherapy. In this study, the functions of RGMb and PD-L2 were examined using the two NSCLC cell lines HCC827 and A549. CRISPR/Cas9 was used to decrease the expression of RGMb and PD-L2, while lentiviral vectors were used to increase their expression. Downstream effects were examined by RT-qPCR and immunoassays. Ectopic expression of RGMb impacted BMP2-induced expression of ID1 and ID2 messenger RNA (mRNA) independently of PD-L2, while RGMb depletion by CRISPR/Cas9 did not affect the BMP2-mediated induction of ID1, ID2, and ID3 mRNA. However, depletion of RGMb resulted in a partial epithelial-mesenchymal transition (EMT) gene expression profile in HCC827 cells, which was not mimicked by PD-L2 depletion. The results show that RGMb is a coregulator of BMP signaling and hence, ID mRNA expression and that RGMb can control the EMT balance in NSCLC cells. However, RGMb appears to exert these functions independently of PD-L2, and accordingly, the PD-1/PD-ligand axis for immune surveillance in NSCLC cells.
In the field of radiation oncology, the benefit of MRI goes beyond that of providing high soft-tissue contrast images for staging and treatment planning. With the recent clinical introduction of ...hybrid MRI linear accelerators it has become feasible to map physiological parameters describing diffusion, perfusion, and relaxation during the entire course of radiotherapy, for example. However, advanced data analysis tools are required for extracting qualified prognostic and predictive imaging biomarkers from longitudinal MRI data. In this study, we propose a new prediction framework tailored to exploit temporal dynamics of tissue features from repeated measurements. We demonstrate the framework using a newly developed decomposition method for tumor characterization.
Two previously published MRI datasets with multiple measurements during and after radiotherapy, were used for development and testing:
-weighted multi-echo images obtained for two mouse models of pancreatic cancer, and diffusion-weighted images for patients with brain metastases. Initially, the data was decomposed using the novel monotonous slope non-negative matrix factorization (msNMF) tailored for MR data. The following processing consisted of a tumor heterogeneity assessment using descriptive statistical measures, robust linear modelling to capture temporal changes of these, and finally logistic regression analysis for stratification of tumors and volumetric outcome.
The framework was able to classify the two pancreatic tumor types with an area under curve (AUC) of 0.999,
< 0.001 and predict the tumor volume change with a correlation coefficient of 0.513,
= 0.034. A classification of the human brain metastases into responders and non-responders resulted in an AUC of 0.74,
= 0.065.
A general data processing framework for analyses of longitudinal MRI data has been developed and applications were demonstrated by classification of tumor type and prediction of radiotherapy response. Further, as part of the assessment, the merits of msNMF for tumor tissue decomposition were demonstrated.
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•Novel data-driven decomposition method (msNMF) identifies MR signal components.•Data-driven decomposition uncovers cell density variations from DWI data.•msNMF of relaxometry data ...leads to edema water fractions in accordance with histology.
MRI can be utilized for quantitative characterization of tissue. To assess e.g. water fractions or diffusion coefficients for compartments in the brain, a decomposition of the signal is necessary. Imposing standard models carries the risk of estimating biased parameters if model assumptions are violated. This work introduces a data-driven multicomponent analysis, the monotonous slope non-negative matrix factorization (msNMF), tailored to extract data features expected in MR signals.
The msNMF was implemented by extending the standard NMF with monotonicity constraints on the signal profiles and their first derivatives. The method was validated using simulated data, and subsequently applied to both ex vivo DWI data and in vivo relaxometry data. Reproducibility of the method was tested using the latter.
The msNMF recovered the multi-exponential signals in the simulated data and showed superiority to standard NMF (based on the explained variance, area under the ROC curve, and coefficient of variation). Diffusion components extracted from the DWI data reflected the cell density of the underlying tissue. The relaxometry analysis resulted in estimates of edema water fractions (EWF) highly correlated with published results, and demonstrated acceptable reproducibility.
The msNMF can robustly separate MR signals into components with relation to the underlying tissue composition, and may potentially be useful for e.g. tumor tissue characterization.
Purpose
The diffusion‐weighted SPLICE (split acquisition of fast spin‐echo signals) sequence employs split‐echo rapid acquisition with relaxation enhancement (RARE) readout to provide images almost ...free of geometric distortions. However, due to the varying T2$$ {}_2 $$‐weighting during k‐space traversal, SPLICE suffers from blurring. This work extends a method for controlling the spatial point spread function (PSF) while optimizing the signal‐to‐noise ratio (SNR) achieved by adjusting the flip angles in the refocusing pulse train of SPLICE.
Methods
An algorithm based on extended phase graph (EPG) simulations optimizes the flip angles by maximizing SNR for a flexibly chosen predefined target PSF that describes the desired k‐space density weighting and spatial resolution. An optimized flip angle scheme and a corresponding post‐processing correction filter which together achieve the target PSF was tested by healthy subject brain imaging using a clinical 1.5 T scanner.
Results
Brain images showed a clear and consistent improvement over those obtained with a standard constant flip angle scheme. SNR was increased and apparent diffusion coefficient estimates were more accurate. For a modified Hann k‐space weighting example, considerable benefits resulted from acquisition weighting by flip angle control.
Conclusion
The presented flexible method for optimizing SPLICE flip angle schemes offers improved MR image quality of geometrically accurate diffusion‐weighted images that makes the sequence a strong candidate for radiotherapy planning or stereotactic surgery.
C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized
C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic ...glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare hyperpolarized 1-
Cpyruvate MRS with simultaneous
F-2-fluoro-2-deoxy-d-glucose (FDG) PET in a cross-sectional study of canine cancer patients.
Canine cancer patients underwent integrated PET/MRI using a clinical whole-body system. Hyperpolarized 1-
Cpyruvate was obtained using dissolution-DNP.
F-FDG PET, dynamic
C MRS,
C MRS Imaging (MRSI) and anatomical
H MRI was acquired from 17 patients. Apparent pyruvate-to-lactate rate constants were estimated from dynamic
C MRS.
F-FDG Standard Uptake Values and maximum 1-
Clactate-to-total-
C ratios were obtained from tumor regions of interest. Following inspection of data, patients were grouped according to main cancer type and linear regression between measures of lactate generation and
F-FDG uptake were tested within groups. Between groups, the same measures were tested for group differences.
The main cancer types of the 17 patients were sarcoma (n = 11), carcinoma (n = 5) and mastocytoma (n = 1). Significant correlations between pyruvate-to-lactate rate constants and
F-FDG uptake were found for sarcoma patients, whereas no significant correlations appeared for carcinoma patients. The sarcoma patients showed a non-significant trend towards lower
F-FDG uptake and higher lactate generation than carcinoma patients. However, the ratio of lactate generation to
F-FDG uptake was found to be significantly higher in sarcoma as compared to carcinoma. The results were found both when lactate generation was estimated as an apparent pyruvate-to-lactate rate constant from dynamic
C MRS and as an 1-
Clactate to total
C ratio from
C MRSI.
A comparison of hyperpolarized 1-
Cpyruvate MRS with simultaneous
F-FDG PET indicate that lactate generation and
F-FDG uptake in cancers can be related and that their relation depend on cancer type. This finding could be important for the interpretation and eventual clinical implementation of hyperpolarized
C. In addition, the differences between the two modalities may allow for better metabolic phenotyping performing hybrid imaging in the form of hyperPET.
AIM: Hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging (MRSI) is a real-time metabolic imaging technique, which can be combined with positron emission tomography (PET). In this ...pilot study, we explore the potential of combined hyperpolarized 13C-MRSI and FDG-PET for imaging of infection. METHODS: Three pigs were inoculated with S. aureusbacteria in the right tibia and saline in the left tibial bone. FDG-PET, 1H-MRI and 13C-MRSI was performed using a clinical whole-body PET/MR system (Siemens Biograph mMR, Erlangen, Germany). Hyperpolarized13C-pyruvate was prepared using a SpinLab System (GE Healthcare, Pittsburgh, PA, USA). 13C-lactate to 13C-pyruvate ratio and FDG SUV was reported in anatomical regions of interest covering bone and regions of inflammation and abscess defined on 1H-MRI. Histopathological examination was performed of both legs. RESULTS: An abscess was observed outside the right (infected bone) on 1H-MRI and confirmed by histopathology. In the abscess the 13C-lactate to 13C-pyruvate ratio was increased as compared to the inflammatory region of the control leg. 18F-FDG uptake showed no clear trend when comparing abscess versus inflammation, but showed an increase considering the infected bone versus the control. In the abscess, the FDG-PET signal distribution had highest intensity in the abscess membrane, whereas the maximum of the13C lactate ratio appears in the abscess cavity. DISCUSSION: The apparent different spatial enhancement pattern of FDG uptake and 13C lactate ratio in abscess suggests that they are independent biomarkers and that hyperpolarized 13C-MRSI is a method with potential for clinical imaging of infection and treatment response.
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