BACKGROUND:A certain proportion of patients with locally advanced rectal cancer experience complete response after undergoing neoadjuvant chemoradiotherapy. These patients might be suitable for a ...conservative “watch and wait” approach, avoiding high-morbidity surgery. Texture analysis is a new modality that can assess heterogeneity in medical images by statistically analyzing gray-level intensities on a pixel-by-pixel basis. This study hypothesizes that texture analysis of magnetic resonance images can identify patients with a complete response.
OBJECTIVE:This study aims to determine whether texture analysis of magnetic resonance images as a quantitative imaging biomarker can accurately identify patients with complete response.
DESIGN:This is a retrospective diagnostic accuracy study.
SETTINGS:This study was conducted at Colchester General Hospital, January 2003 to 2014.
PATIENTS:All patients diagnosed with locally advanced rectal cancer who underwent long-course chemoradiotherapy, had a posttreatment magnetic resonance scan, and underwent surgery are included.
INTERVENTION:Texture analysis was extracted from T2-weighted magnetic resonance images of the rectal cancer.
MAIN OUTCOME MEASURES:Textural features that are able to identify complete responders were identified by a Mann-Whitney U test. Their diagnostic accuracy in identifying complete responders was determined by the area under the receiver operator characteristics curve. Cutoff values were determined by the Youden index. Pathology was the standard of reference.
RESULTS:One hundred fourteen patients with first posttreatment MRI scans (6.2 weeks after completion of neoadjuvant treatment) were included. Sixty-eight patients had a second posttreatment scan (10.4 weeks). With no filtration, mean (p = 0.033), SD (p = 0.048), entropy (p = 0.007), and skewness (p = 0.000) from first posttreatment scans, and SD (p = 0.042), entropy (p = 0.014), mean of positive pixels (p = 0.032), and skewness (p = 0.000) from second posttreatment scans were all able to identify complete response. Area under the curve ranged from 0.750 to 0.88.
LIMITATIONS:Texture analysis of MRI is a new modality; therefore, further studies are necessary to standardize the methodology of extraction of texture features, timing of scans, and acquisition parameters.
CONCLUSIONS:Texture analysis of MRI is a potentially significant imaging biomarker that can accurately identify patients who have experienced complete response and might be suitable for a nonsurgical approach. (Cinicaltrials.gov:NCT02439086). See Video Abstract at http://links.lww.com/DCR/A760.
We report a case series of biopsy-proven reactive axillary lymph nodes, which were avid on FDG PET/CT in breast cancer patients post COVID-19 vaccination. With 4 cases presenting in a consecutive ...10-day period, it became apparent that metabolically active axillary lymphadenopathy is an adverse effect of COVID-19 vaccines, currently being deployed worldwide. This may lead to patients undergoing unnecessary biopsy. We have started taking a COVID-19 vaccine status history before PET/CT. If enlarged/metabolically active axillary nodes are identified in the ipsilateral vaccinated arm, then axillary ultrasound at 4 weeks is suggested.
There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA).
To determine the profile of biomarkers relevant to neurodegenerative ...disease in the CSF of patients with CAA.
We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer's disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service.
We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for Aβ38, Aβ40, Aβ42, and sAβPPβ. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF Aβ42, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an "AD-like" profile.
CAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed.
Purpose
To assess the potential role of computed tomography (CT) texture analysis (CTTA) in identifying vulnerable patients with carotid artery atherosclerosis.
Methods
In this case-control pilot ...study, 12 patients with carotid atherosclerosis and a subsequent history of transient ischemic attack or stroke were age and sex matched with 12 control cases with asymptomatic carotid atherosclerosis (follow-up time 103.58 ± 9.2 months). CTTA was performed using a commercially available research software package (TexRAD) by an operator blinded to clinical data. CTTA comprised a filtration-histogram technique to extract features at different scales corresponding to spatial scale filter (fine = 2 mm, medium = 3 mm, coarse = 4 mm), followed by quantification using histogram-based statistical parameters: mean, kurtosis, skewness, entropy, standard deviation, and mean value of positive pixels. A single axial slice was selected to best represent the largest cross-section of the carotid bifurcation or the greatest degree of stenosis, in presence of an atherosclerotic plaque, on each side.
Results
CTTA revealed a statistically significant difference in skewness between symptomatic and asymptomatic patients at the medium (0.22 ± 0.35 vs − 0.18 ± 0.39,
p
< 0.001) and coarse (0.23 ± 0.22 vs 0.03 ± 0.29,
p
= 0.003) texture scales. At the fine-texture scale, skewness (0.20 ± 0.59 vs − 0.18 ± 0.58,
p
= 0.009) and standard deviation (366.11 ± 117.19 vs 300.37 ± 82.51,
p
= 0.03) were significant before correction.
Conclusion
Our pilot study highlights the potential of CTTA to identify vulnerable patients in stroke and TIA. CT texture may have the potential to act as a novel risk stratification tool in patients with carotid atherosclerosis.
Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is a potent inhibitor ...of PI3K/mTOR.A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study of omipalisib in subjects with IPF was conducted (NCT01725139) to test safety, tolerability, pharmacokinetics and pharmacodynamics. Omipalisib was dosed at 0.25 mg, 1 mg and 2 mg twice daily for 8 days in four cohorts of four subjects randomised 3:1 to receive omipalisib or placebo (two cohorts received 2 mg twice daily).17 subjects with IPF were enrolled. The most common adverse event was diarrhoea, which was reported by four participants. Dose-related increases in insulin and glucose were observed. Pharmacokinetic analysis demonstrated that exposure in the blood predicts lung exposure. Exposure-dependent inhibition of phosphatidylinositol 3,4,5 trisphosphate and pAKT confirmed target engagement in blood and lungs.
F-2
fluoro-2-deoxy-d-glucose(FDG)-positron emission tomography/computed tomography scans revealed an exposure-dependent reduction in
F-FDG uptake in fibrotic areas of the lung, as measured by target-to-background, ratio thus confirming pharmacodynamic activity.This experimental medicine study demonstrates acceptable tolerability of omipalisib in subjects with IPF at exposures for which target engagement was confirmed both systemically and in the lungs.
We thank P-S. Bellaye and co-workers for their considered and insightful response. Given their finding of
18
Ffluoromisonidazole (
18
FF-MISO) uptake in the bleomycin mouse model of fibrosis 1, we ...too were surprised not to demonstrate a similar signal in patients with idiopathic pulmonary fibrosis (IPF). However, as acknowledged, there are other examples of positron emission tomography (PET) tracers, such as cis-4-
18
F-fluoro-
l
-proline, yielding PET signals in animal lung fibrosis models that have not been replicated in humans with fibrotic lung disease 2, 3.
In vivo
PET imaging in IPF patients shows no significant evidence of lung tissue hypoxia
https://bit.ly/3fywY7K
Recently, there has been an increased interest in imaging different pulmonary disorders using PET techniques. Previous work has shown, for static PET/CT, that air content in the lung influences ...reconstructed image values and that it is vital to correct for this 'tissue fraction effect' (TFE). In this paper, we extend this work to include the blood component and also investigate the TFE in dynamic imaging. CT imaging and PET kinetic modelling are used to determine fractional air and blood voxel volumes in six patients with idiopathic pulmonary fibrosis. These values are used to illustrate best and worst case scenarios when interpreting images without correcting for the TFE. In addition, the fractional volumes were used to determine correction factors for the SUV and the kinetic parameters. These were then applied to the patient images. The kinetic parameters K1 and Ki along with the static parameter SUV were all found to be affected by the TFE with both air and blood providing a significant contribution to the errors. Without corrections, errors range from 34-80% in the best case and 29-96% in the worst case. In the patient data, without correcting for the TFE, regions of high density (fibrosis) appeared to have a higher uptake than lower density (normal appearing tissue), however this was reversed after air and blood correction. The proposed correction methods are vital for quantitative and relative accuracy. Without these corrections, images may be misinterpreted.
We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging ...parameters in patients with non-small cell lung cancer (NSCLC).
The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 ± 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 ± 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUVmax). The mean follow-up periods were 22.6 ± 13.3 months and 28.5± 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan-Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence.
Univariate analysis revealed that tumor CT-derived heterogeneity (P < 0.001), PET-derived heterogeneity (P = 0.003), CT-derived permeability (P = 0.002), and stage (P < 0.001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUVmax did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P = 0.021), stage (P = 0.001), and permeability (P < 0.001) were independent survival predictors. These predictors were independent of patient treatment.
Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC.
The impact of positron range on PET image reconstruction has often been investigated as a blurring effect that can be partly corrected by adding an element to the PET system matrix in the ...reconstruction, usually based on a Gaussian kernel constructed from the attenuation values. However, the physics involved in PET is more complex. In regions where density does not vary, positron range indeed involves mainly blurring. However, in more heterogeneous media it can cause other effects. This work focuses on positron range in the lungs and its impact on quantification, especially in the case of pathologies such as cancer or pulmonary fibrosis, for which the lungs have localised varying density. Using Monte Carlo simulations, we evaluate the effects of positron range for multiple radionuclides (18F, 15O, 68Ga, 89Zr, 82Rb, 64Cu and 124I) as, for novel radiotracers, the choice of the labelling radionuclide is important. The results demonstrate quantification biases in highly heterogeneous media, where the measured uptake of high-density regions can be increased by the neighbouring radioactivity from regions of lower density, with the effect more noticeable for radionuclides with high-energy positron emission. When the low-density regions are considered to have less radioactive uptake (e.g. due to the presence of air), the effect is less severe.
While the pursuit of better time resolution in positron emission tomography (PET) is rapidly evolving, little work has been performed on time of flight (TOF) image quality at high time resolution in ...the presence of modelling inconsistencies. This works focuses on the effect of using the wrong attenuation map in the system model, causing perturbations in the reconstructed radioactivity image. Previous work has usually considered the effects to be local to the area where there is attenuation mismatch, and has shown that the quantification errors in this area tend to reduce with improved time resolution. This publication shows however that errors in the PET image at a distance from the mismatch increase with time resolution. The errors depend on the reconstruction algorithm used. We quantify the errors in the hypothetical case of perfect time resolution for maximum likelihood reconstructions. In addition, we perform reconstructions on simulated and patient data. In particular, for respiratory-gated reconstructions from a wrong attenuation map, increased errors are observed with improved time resolutions in areas close to the lungs (e.g. from 13.3% in non-TOF to up to 20.9% at 200 ps in the left ventricle).
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