Surrogate Imaging Research Articles

Magnetic resonance radiomics features and prognosticators in different molecular subtypes of pediatric Medulloblastoma.

PurposeMedulloblastoma (MB) is a highly malignant pediatric brain tumor. In the latest classification, medulloblastoma is divided into four distinct groups: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. We analyzed the magnetic resonance imaging radiomics features to find the imaging surrogates of the 4 molecular subgroups of MB.Material and methodsFrozen tissue, imaging data, and clinical data of 38 patients with medulloblastoma were included from Taipei Medical University Hospital and Taipei Veterans General Hospital. Molecular clustering was performed based on the gene expression level of 22 subgroup-specific signature genes. A total 253 magnetic resonance imaging radiomic features were generated from each subject for comparison between different molecular subgroups.ResultsOur cohort consisted of 7 (18.4%) patients with WNT medulloblastoma, 12 (31.6%) with SHH tumor, 8 (21.1%) with Group 3 tumor, and 11 (28.9%) with Group 4 tumor. 8 radiomics gray-level co-occurrence matrix texture (GLCM) features were significantly different between 4 molecular subgroups of MB. In addition, for tumors with higher values in a gray-level run length matrix feature—Short Run Low Gray-Level Emphasis, patients have shorter survival times than patients with low values of this feature (p = 0.04). The receiver operating characteristic analysis revealed optimal performance of the preliminary prediction model based on GLCM features for predicting WNT, Group 3, and Group 4 MB (area under the curve = 0.82, 0.72, and 0.78, respectively).ConclusionThe preliminary result revealed that 8 contrast-enhanced T1-weighted imaging texture features were significantly different between 4 molecular subgroups of MB. Together with the prediction models, the radiomics features may provide suggestions for stratifying patients with MB into different risk groups.

Radiogenomics in brain, breast, and lung cancer: opportunities and challenges.

.The field of radiogenomics largely focuses on developing imaging surrogates for genomic signatures and integrating imaging, genomic, and molecular data to develop combined personalized biomarkers for characterizing various diseases. Our study aims to highlight the current state-of-the-art and the role of radiogenomics in cancer research, focusing mainly on solid tumors, and is broadly divided into four sections. The first section reviews representative studies that establish the biologic basis of radiomic signatures using gene expression and molecular profiling information. The second section includes studies that aim to non-invasively predict molecular subtypes of tumors using radiomic signatures. The third section reviews studies that evaluate the potential to augment the performance of established prognostic signatures by combining complementary information encoded by radiomic and genomic signatures derived from cancer tumors. The fourth section includes studies that focus on ascertaining the biological significance of radiomic phenotypes. We conclude by discussing current challenges and opportunities in the field, such as the importance of coordination between imaging device manufacturers, regulatory organizations, health care providers, pharmaceutical companies, academic institutions, and physicians for the effective standardization of the results from radiogenomic signatures and for the potential use of these findings to improve precision care for cancer patients.

Pretreatment 18F-FDG PET/CT Imaging Predicts the KRAS/NRAS/BRAF Gene Mutational Status in Colorectal Cancer.

Objective To investigate the association between KRAS/NRAS/BRAF mutations and metabolic parameters of pretreatment 18F-FDG PET/CT in colorectal cancer (CRC). Methods A total of 85 patients with CRC were included in the study. PET/CT was performed in all the patients before surgery. The histopathological examination and analysis of the gene mutational status of the primary tumor were conducted. The associations among clinical features, PET metabolic parameters, and the gene mutational status were investigated. Moreover, receiver operating characteristic (ROC) curves for maximum standard uptake value (SUVmax) of the primary tumor were generated along with analysis of the target tissue to nontarget tissue ratio (T/NT) for predicting the efficacy of KRAS/NRAS/BRAF mutations in CRC. Finally, the corresponding area under the curve, the optimal cutoff value, and the corresponding sensitivity and specificity were obtained. Results The mutation rate of KRAS/NRAS/BRAF was 54.12% (46/85). In addition, both SUVmax and T/NT were significantly higher in the KRAS/NRAS/BRAF-mutation groups compared to the wild-type group (15.88 ± 6.71 vs. 12.59 ± 5.79, 8.04 ± 3.03 vs. 6.38 ± 2.80; P=0.012 and 0.004, respectively). Results from the ROC curve also showed that the cutoff values for T/NT and SUVmax were 5.14 and 12.40, respectively, while the predictive accuracy was 0.682 and 0.647, respectively. On the other hand, the sensitivity was 91.30% and 65.22% while the specificity was 43.59% and 64.10%, respectively. Moreover, univariate analysis showed that the KRAS/NRAS/BRAF mutation was not significantly associated with gender, age, lesion location, tumor length, pathological type, tissue differentiation, and UICC staging (all P > 0.05). Conclusion T/NT ratio and SUVmax could be the potential surrogate imaging indicators to predict the KRAS/NRAS/BRAF mutational status in CRC patients.

Volumetric measurement of the hippocampus in a series of patients with Alzheimer disease

BackgroundHippocampal volume is recognised as a surrogate imaging biomarker for the study of Alzheimer's disease (AD). However, in Cuba there are no antecedents of its use. The objective of this research was to establish an automatic hippocampal segmentation procedure to study a sample of Cuban subjects diagnosed with possible mild or moderate AD. MethodologyA total of 104 subjects with mean ages of 73.77 ± 6.74 years participated. Imaging for the calculation of hippocampal volumes and asymmetry index (AI) was performed with a Siemens Magnetom Allegra 3T scanner using an MP-RAGE sequence. Volumes were obtained manually and automatically using Amira 5.3 and FreeSurfer 6.0 software, respectively. The results of both methods were statistically compared. ResultsThe steps for hippocampal volumetric quantification were established for these methods. Comparison between them showed high concordance (ICC = 0.95) for both hippocampi. Therefore, there were no significant differences between them. The mean right (2961.84 ± 552.70 mm3) and left (2892.68 ± 536.6 mm3) volumes of the subjects were obtained. These volumes and the asymmetry index were significantly different with respect to a sample of healthy subjects with (p = 0.00001) and (p = 0.003) respectively; and similar to those obtained in a sample of subjects with AD in Latin America. ConclusionsA procedure for automated volumetric quantification of the hippocampus was established. This allowed the study of a Cuban sample with possible AD. This constitutes a previous step to longitudinally evaluate the effectiveness of new Cuban drugs.

Deep Learning With Radiogenomics Towards Personalized Management of Gliomas.

A state-of-the-art interdisciplinary survey on multi-modal radiogenomic approaches is presented involving applications to the diagnosis and personalized management of gliomas a common kind of brain tumors through noninvasive imaging integrated with genomic information. It encompasses mining tumor radioimages employing deep learning for the automated extraction of relevant features from the segmented volume of interest (VOI). Gene expression values from surgically extracted tumor tissues are often simultaneously analyzed to determine patient specific features. Association between genomic and radiomic features are also explored in some cases to determine the imaging surrogates. Deep learning and transfer learning are typically exploited for efficient knowledge discovery and decision-making. Some studies on survival prediction ensemble learning and interactive learning are also included. The literature mainly focuses on magnetic resonance imaging (MRI) data of the brain for learning and validation and generally involves the NIH TCIA and TCGA repositories as well as the BraTS Challenge databases.

Spinal Cord Cervical and Thoracic Gray Matter Atrophy – an emerging imaging surrogate for Amyotrophic Lateral Sclerosis (4099)

Spinal Cord Cervical and Thoracic Gray Matter Atrophy – an emerging imaging surrogate for Amyotrophic Lateral Sclerosis (4099)

Diagnostic value of DWI-MRI for the detection of acute plaques in the relapse phase of multiple sclerosis

Background. The 2010 revision of the McDonald criteria, widely used for the diagnosis of multiple sclerosis (MS), has established that dissemination in time (DIT) can be demonstrated by the simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing plaques on a single magnetic resonance imaging (MRI). When the use of gadolinium contrast agents is contraindicated, diffusion-weighted imaging (DWI) is utilized to confirm diffusion alterations in active inflammatory plaques. This study intended to examine whether DWI can be a viable alternative to contrast-enhanced T1-weighted imaging for demonstrating DIT in MS. Material and methods.We assessed 30 previously diagnosed MS patients during acute relapse (based on the 2010 McDonald criteria) and evaluated their brain MRI via DWI‚ contrast-enhanced T1-weighted imaging, and FLAIR sequences. Asymptomatic plaques were defined as either hyperintense or non-hyperintense in DWI and enhancing or non-enhancing in T1GAD-MRI. Statistical indices for the prediction of plaque enhancement in T1 GAD-MRI via DWI-MRI were calculated and compared. Results. The 30 participants in our study had a total of 925 demyelinating plaques that were larger than 3mm in size and presented to be hyperintense in FLAIR-MRI. Diffusion hyperintensity and plaque enhancement were significantly correlated. The sensitivity‚ specificity, positive predictive value‚ negative predictive value, and accuracy of DWI were calculated to be 69.66%‚ 99.76%‚ 96.88%‚ 96.86%, and 96.86%, respectively. Conclusions. Hyperintense DWI findings do not necessarily overlap with contrast enhancements in T1 GAD-MRI. DWI was shown to produce a higher rate of false-positive results. Our study concludes that although T1 GAD-MRI should not be replaced by DWI to determine DIT due to its lower specificity, DWI’s continued use as a surrogate screening imaging sequence whenever the use of T1GAD-MRI is of concern is not without its merits.

Electron Beam CT: A Historical Review.

OBJECTIVE. At its advent, CT was too slow to image the heart. Temporal resolution improved with electron beam CT (EBCT); subsequently, the heart could be imaged, eventually leading to the discovery of prognostic information obtained from the coronary calcium score. In the early 2000s, EBCT was replaced by MDCT. In this review, we discuss the rise and fall of EBCT and explore its legacy in cardiac imaging. CONCLUSION. Although MDCT rendered EBCT obsolete, EBCT leaves a legacy in cardiac imaging regarding both diagnosis and prognosis. The creators of MDCT emulated the strengths of EBCT and learned from its weaknesses. Moreover, EBCT showed that imaging surrogates can predict outcomes, and the origins of substrate-guided treatment can be traced to EBCT.

Associations of Brain Atrophy and Cerebral Iron Accumulation at MRI with Clinical Severity in Wilson Disease.

Background Abnormal findings at brain MRI in patients with neurologic Wilson disease (WD) are characterized by signal intensity changes and cerebral atrophy. T2 signal hypointensities and atrophy are largely irreversible with treatment; their relationship with permanent disability has not been systematically investigated. Purpose To investigate associations of regional brain atrophy and iron accumulation at MRI with clinical severity in participants with neurologic WD who are undergoing long-term anti-copper treatment. Materials and Methods Participants with WD and controls were compared in a prospective study performed from 2015 to 2019. MRI at 3.0 T included three-dimensional T1-weighted and six-echo multigradient-echo pulse sequences for morphometry and quantitative susceptibility mapping, respectively. Neurologic severity was assessed with the Unified WD Rating Scale (UWDRS). Automated multi-atlas segmentation pipeline with dual contrast (susceptibility and T1) was used for the calculation of volumes and mean susceptibilities in deep gray matter nuclei. Additionally, whole-brain analysis using deformation and surface-based morphometry was performed. Least absolute shrinkage and selection operator regression was used to assess the association of regional volumes and susceptibilities with the UWDRS score. Results Twenty-nine participants with WD (mean age, 47 years ± 9 [standard deviation]; 15 women) and 26 controls (mean age, 45 years ± 12; 14 women) were evaluated. Whole-brain analysis demonstrated atrophy of the deep gray matter nuclei, brainstem, internal capsule, motor cortex and corticospinal pathway, and visual cortex and optic radiation in participants with WD (P < .05 at voxel level, corrected for family-wise error). The UWDRS score was negatively correlated with volumes of putamen (r = -0.63, P < .001), red nucleus (r = -0.58, P = .001), globus pallidus (r = -0.53, P = .003), and substantia nigra (r = -0.50, P = .006) but not with susceptibilities. Only the putaminal volume was identified as a stable factor associated with the UWDRS score (R2 = 0.38, P < .001) using least absolute shrinkage and selection operator regression. Conclusion Individuals with Wilson disease (WD) had widespread brain atrophy most pronounced in the central structures. The putaminal volume was associated with the Unified WD Rating Scale score and can be used as a surrogate imaging marker of clinical severity. © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Du and Bydder in this issue.

Abstract P374: Dolichoectacic Features of Basilar Artery Serve an Imaging Surrogate of Branch Artery Disease in Patients With Pontine Infarcts

Background: The arterial pathology underlying recent small subcortical infarctions (historically known as lacunar stroke) is heterogenous and includes lipohyalinosis, branch artery atherosclerosis or embolism. Although the use of high-resolution imaging studies directed to vessel wall might be helpful in teasing out these different pathologies, more readily available imaging surrogates such as size or spatial characteristics of the ischemic lesion are used for this purpose in clinical practice. Herein, we determined the distribution of dolichoectacic features of basilar artery in patients presenting with pontine penetrator artery stroke with different underlying occlusive pathologies. Methods: The dolichoectacic features of basilar artery were retrospectively evaluated according to Smoker’s criteria (diameter: &gt;4.5 mm, laterality: more lateral to the lateral margin of clivus or dorsum sellae, and height of bifurcation: at least at the level of third ventricular floor) on CT angiography in ischemic stroke patients with a single penetrator artery occlusion in the pons. Patients with basilar artery pathologies such stenosis, dissection, or apparent dolichoectasia were excluded. Ischemic lesions extending to the surface of pontine base on DWI were judged to be secondary to branch artery occlusion, rather than lipohyalinosis. Results: Out of 122 patients, 68 (56%) had at least one feature suggestive of basilar artery dolichoectasia. Patients with lateral deviation of basilar artery were more likely to harbor infarcts extending to pontine surface (69% vs. 50%); no such relationship was identified for other imaging markers of dolichoectasia. After adjustment for age, gender and vascular risk factors, lateral deviation of the basilar artery remained significantly associated with an infarct pattern suggestive of branch artery occlusion (OR=2.8, 95%CI 1.1-7.3; p=0.031). There was also a tendency for ischemic lesions to be located on the ipsilateral side of the lateral deviation (63%; p=0.081). Conclusion: Our findings highlight that lateral displacement of basilar artery, an imaging feature of basilar dolichoectasia, can be used as an additional surrogate marker of branch artery pathology in patients with pontine penetrator artery infarction.

Diagnostic accuracy of chest computed tomography in improving the false negative rate as compared to reverse transcriptase polymerase chain reaction in coronavirus disease 2019 pneumonia: A cross sectional analysis of 348 cases from India.

Background:Early differentiation between emergency department (ED) patients with and without coronavirus disease 2019 (COVID-19) is very important. The diagnosis of COVID-19 depends on real-time reverse transcriptase polymerase chain reaction (RT-PCR). On imaging, computed tomography (CT) manifestations resemble those seen in viral pneumonias, with multifocal ground-glass opacities and consolidation in a peripheral distribution being the most common findings. Although these findings lack specificity for COVID-19 diagnosis on imaging grounds, CT could be used to provide objective assessment about the extension of the lung opacities, which could be used as an imaging surrogate for disease burden. We set out to investigate the diagnostic accuracy of chest CT scanning in detecting COVID-19 in a population with suspected COVID-19 patients.Materials and Methods:In this cross-sectional single-center study performed on 348 cases with clinical suspicion of COVID-19, all adult symptomatic ED patients had both a CT scan and a PCR upon arrival at. CT results were compared with PCR test (s) and diagnostic accuracy was calculated.Results:Between February 15, 2020, and June 30, 2020, 348 symptomatic patients were included. In total, 62.3% of patients had a positive PCR and 69.8% had a positive CT, resulting in a sensitivity of 94.2%, specificity of 76.7%, likelihood ratio (LR) of +2.94 and (LR) −0.18. The sensitivity of the CT tended to be higher in those with acute respiratory distress syndrome (100.0%, P = 0.017) and severe COVID-19 (98.5%, P = 0.027) than in patients with mild (82.5%, P = 0.047) and moderate COVID-19 (89.3%, P = 0.039). The diagnostic ability of chest CT was found to be high with 86.3% concordance between findings of CT and PCR. In 48 (13.7%) patients, discordant findings between CT and PCR were observed. In most cases, the CT scan was considered suspicious for COVID-19, while the PCR was negative (37/48, 77.0%). In the majority of these, the diagnosis at discharge was pulmonary infection (n = 26; 54.1%).Conclusion:The accuracy of chest CT in symptomatic COVID suspect patients is high, but when used as a single diagnostic test, CT cannot accurately diagnose or exclude COVID-19. Therefore, we recommend a combination of both CT and RT-PCR for future follow-up, management, and medical surveillance.

Diagnostic accuracy and false-positive rate of chest CT as compared to RT-PCR in coronavirus disease 2019 (COVID-19) pneumonia: A prospective cohort of 612 cases from India and review of literature.

Background:At present, the diagnosis of COVID-19 depends on real-time reverse transcriptase polymerase chain reaction (RT-PCT). On imaging, computed tomography (CT) manifestations resemble those seen in viral pneumonias, with multifocal ground-glass opacities and consolidation in a peripheral distribution being the most common findings. Although these findings lack specificity for COVID-19 diagnosis on imaging grounds, CT could be used to provide objective assessment about the extension of the lung opacities, which could be used as an imaging surrogate for disease burden. Chest CT scan may be helpful in early diagnosing of COVID-19.Objective:The current study investigated the diagnostic accuracy and false-positive rate of chest CT in detecting COVID-19 pneumoniain a population with clinical suspicion using RT-PCR testing as reference standard.Materials and Methods:In this prospective single centerstudy performed on 612 cases with clinical suspicion of COVID-19, all adult symptomatic ED patients had both a CT scan and a PCR upon arrival at the hospital. CT results were compared with PCR test (s) and diagnostic accuracy was calculated.Results:Between February 15, 2020 to July 15, 2020, 612 symptomatic ED patients were included. In total, 78.5% of patients had a positive PCR and 82.8% a positive CT, resulting in a sensitivity of 94.2%, specificity 76.4%, likelihood ratio (LR) + 2.94 and (LR) - 0.18. The PPV was 76.7% and NPV 94.1%. The sensitivity of the CT tended to be higher (100.0%) in those with severe risk pneumonia than in patients with low/medium risk pneumonia (90.3%, P = 0.42). In patients with sepsis, sensitivity was significantly higher than in those without sepsis (99.5 vs. 63.5%, P < 0.001). The diagnostic ability of chest CT was found to be rather high with 92.1%, concordance rate between findings of CT and PCR. In 48 (7.8%) patients discordant findings between CT and PCR were observed. The positive predictive values (PPV) and accuracy of chest CT in diagnosing COVID-19 were higher in patients ≥60 years than that in patients <60 years (P = 0.001 and 0.004, respectively). The specificity and NPV of chest CT in diagnosing COVID-19 were greater for women than that for men (P = 0.007 and 0.03, respectively); and no difference existed for sensitivity, PPV and accuracy (P = 0.43, 0.69 and 0.31, respectively). In most cases, the CT scan was considered suspicious for COVID-19, while the PCR was negative (37/48, 70.8%). In the majority of these, the diagnosis at discharge was pulmonary infection (n = 26; 74.3%). The current study included repeated PCRs and explored discordant test results, which showed that in about 45.9% of patients with false-positive CT scans, other viral pathogens were detected. The false-positive rate of CT findings in the diagnosis of COVID-19 pneumonia was 7.2%.Conclusion:High diagnostic accuracy of chest CT findings with typical and relatively atypical CT manifestations of COVID-19 leads to a low rate of missed diagnosis. Normal chest CT can be found in RT-PCR positive COVID-19 cases, and typical CT manifestations can be found in RT-PCR negative cases. Therefore, a combination of both CT and RT-PCR for future follow-up, management and medical surveillance is recommended considering the false-positive results of chest CT in the diagnosis of COVID-19 pneumonia.

Cervical and intracranial artery dissections.

This review summarizes recent therapeutic advances in cervical (CeAD) and intracranial artery dissection (IAD) research. Despite unproven benefits, but in the absence of any signal of harm, in patients, with acute ischemic stroke attributable to CeAD, intravenous thrombolysis and, in case of large-vessel occlusion, endovascular revascularization should be considered. Future research will clarify which patients benefit most from either treatment modality. For stroke prevention, the recently published randomized controlled TREAT-CAD study showed that, against the initial hypothesis, aspirin was not shown non-inferior to anticoagulation with vitamin K antagonists (VKAs). With the results of two randomized controlled trials (CADISS and TREAT-CAD) available now, the evidence to consider aspirin as the standard therapy of CeAD is weak. Further analyses might clarify whether the assumption supports, in particular, that patients presenting with cerebral ischemia, clinical or subclinical with magnetic resonance imaging surrogates, might benefit most from VKA treatment. In turn, it remains to be shown, whether in CeAD patients presenting with pure local symptoms and without hemodynamic compromise, antiplatelets are sufficient, and whether a dual antiplatelet therapy during the first weeks of treatment is recommendable. The observation that ischemic strokes occurred (or recurred) very early after CeAD diagnosis, consistently across randomized and observational studies, supports the recommendation to start antithrombotic treatment immediately, whatever antithrombotic agent is chosen in each individual case. The lack of a license for the use in CeAD patients and the paucity of data are still arguments against the use of direct oral anticoagulants in CeAD. Nevertheless, due to their beneficial safety and efficacy profile proven in atrial fibrillation, these agents are a worthwhile treatment option to be tested in further CeAD treatment trials. In IAD, the experience with the use of antithrombotic agents is limited. As the risk of suffering intracranial hemorrhage is higher in IAD than in CeAD, the use of antithrombotic therapy in IAD remains controversial.

Comparison between optical frequency domain imaging and intravascular ultrasound in PCI guidance for Biolimus A9 eluting stent implantation

Abstract Background It has been reported that intravascular ultrasound (IVUS) guided PCI reduced a risk of major adverse cardiac event compared to conventional angiography guided PCI, while comparison between IVUS-guided and optical frequency domain imaging (OFDI)-guided PCI specifically in long-term clinical outcomes (&amp;gt;1 year) has been unexplored. Purpose We sought to compare imaging surrogates at 8 months and clinical outcomes beyond 1 year after drug-eluting stent implantation between IVUS and OFDI guidance. Methods The MISTIC-1 is a prospective, multi-centre, single-blinded, randomised-controlled, non-inferiority trial comparing OFDI-guided and IVUS-guided PCI using Biolimus A9 eluting Nobori stent. We enrolled patients with stable coronary artery disease who have symptoms or clinically relevant myocardial ischemia. Stent landing zones were selected in the most normal looking sites with largest lumen and without percentage plaque area &amp;gt;50% in IVUS group while without lipidic plaque of &amp;gt;2 quadrants or suggestive thin-cap fibroatheroma in OFDI group. Stent sizing was based on external elastic lamina (EEL) in IVUS group, while by taking 10% or 0.25mm larger than mean lumen diameter at reference sites in OFDI group. Stent optimisation with in-stent minimum lumen area ≥80% of the average lumen area at proximal and distal reference sites was encouraged in both groups. Primary efficacy endpoint is in-segment minimum lumen area (MLA) assessed by OFDI at 8 months. Secondary safety endpoint is a composite of cardiovascular death, target vessel myocardial infarction, or target lesion revascularisation. Based on the assumption that mean in-segment MLA at follow-up was 4.5mm2 with a standard deviation of 2.0mm2 in the control (IVUS) group and a non-inferiority limit of 1.2mm2 for OFDI group, sample size was estimated as 48 cases in each group with 5% type I error and 90% statistical power. Results Since June-2014 and August-2016, we prospectively enrolled 109 patients (mean age 70 years, male 78%) with 126 lesions. Baseline patient and lesion characteristics were well balanced and average nominal size and length of stent used did not differ between OFDI-guided and IVUS-guided PCI (3.0 and 19.1mm vs. 3.1 and 19.3mm, respectively). Post-procedural minimum stent area was 6.24mm2 in OFDI group and 6.72mm2 in IVUS group (p=0.20). At 8-month follow-up, in-segment MLA was 4.56mm2 in OFDI group and 4.13mm2 in IVUS group (P for non-inferiority &amp;lt;0.001). During the follow-up (median 4.5 years [1654 days]), incidence rates of major adverse cardiac event were comparable between the two groups (7.4% in OFDI group and 7.3% in IVUS group, hazard ratio 0.96, 95% CI 0.24–3.83, p=0.95). No definite or probable stent thrombosis were documented in both groups. Conclusion OFDI-guided PCI demonstrated comparable results in achieving satisfactory imaging surrogates as well as long-term clinical outcomes after newer generation DES implantation as compared to IVUS-guided PCI. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Suzuken Memorial Foundation

PET imaging of meningioma with 18F-FLT: a predictor of tumour progression.

We have previously reported that PET with 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) provides a non-invasive assessment of cell proliferation in vivo in meningiomas. The purpose of this prospective study was to evaluate the potential of 18F-FLT PET in predicting subsequent tumour progression in asymptomatic meningiomas. Forty-three adult patients harbouring 46 MRI-presumed (n = 40) and residual meningiomas from previous surgery (n = 6) underwent a 60-min dynamic 18F-FLT PET scan prior to radiological surveillance. Maximum and mean tumour-to-blood ratios (TBRmax, TBRmean) of tracer radioactivity were calculated. Tumour progression was defined according to the latest published trial end-point criteria for bidimensional (2D) and corresponding yet exploratory volumetric measurements from the Response Assessment of Neuro-Oncology (RANO) workgroup. Independent-sample t-test, Pearson correlation coefficient, Cox regression, and receiver operating characteristic (ROC) curve analyses were used whenever appropriate. The median follow-up time after 18F-FLT PET imaging was 18 months (range 5-33.5 months). A high concordance rate (91%) was found with regard to disease progression using 2D-RANO (n = 11) versus volumetric criteria (n = 10). Using 2D-RANO criteria, 18F-FLT uptake was significantly increased in patients with progressive disease, compared to patients with stable disease (TBRmax, 5.5 ± 1.3 versus 3.6 ± 1.1, P < 0.0001; TBRmean, 3.5 ± 0.8 versus 2.4 ± 0.7, P < 0.0001). ROC analysis yielded optimal thresholds of 4.4 for TBRmax [sensitivity 82%, specificity 77%, accuracy 78%, and area under curve (AUC) 0.871; P < 0.0001] and 2.8 for TBRmean (sensitivity 82%, specificity 77%, accuracy 78%, AUC 0.848; P = 0.001) for early differentiation of patients with progressive disease from patients with stable disease. Upon excluding patients with residual meningioma or patients with stable disease with less than 12 months follow-up, the thresholds remained unchanged with similar diagnostic accuracies. Moreover, positive correlations were found between absolute and relative tumour growth rates and 18F-FLT uptake (r < 0.513, P < 0.015) that remained similar when excluding patients with residual meningioma or patients with stable disease and shorter follow-up period. Diagnostic accuracies were slightly inferior at 76% when assessing disease progression using volumetric criteria, while the thresholds remained unchanged. Multivariate analysis revealed that TBRmax was the only independent predictor of tumour progression (P < 0.046), while age, gender, baseline tumour size, tumour location, peritumoural oedema, and residual meningioma had no influence. The study reveals that 18F-FLT PET is a promising surrogate imaging biomarker for predicting subsequent tumour progression in treatment-naïve and asymptomatic residual meningiomas.

Cyclotron-Produced 132La as a PET Imaging Surrogate for Therapeutic 225Ac.

The aim of this work was to explore 132La as a PET imaging surrogate for 225Ac using a DOTA-based, tumor-targeting alkylphosphocholine (NM600). Methods:132La was produced on a biomedical cyclotron. For invivo experiments, mice bearing 4T1 tumors were administered 132La-NM600, and PET/CT scans were acquired up to 24 h after injection. After the last time point, the ex vivo tissue distribution was measured to corroborate the invivo PET data. The ex vivo tissue distribution in mice was determined at 4 and 24 h after injection of 225Ac-NM600. Results: PET/CT images showed elevated, persistent 132La-NM600 uptake in the tumor. Low bone accumulation confirmed the invivo stability of the conjugate. Ex vivo biodistribution studies validated the image-derived quantitative data, and the comparison of the 132La-NM600 and 225Ac-NM600 tissue distributions revealed a similar biodistribution for the 2 radiotracers. Conclusion: These findings suggest that 132La is a suitable imaging surrogate to probe the invivo biodistribution of 225Ac radiotherapeutics.

Tenecteplase (and common sense) in short supply during the COVID ‐19 pandemic

Tenecteplase (and common sense) in short supply during the <scp>COVID</scp> ‐19 pandemic

Invited Commentary: Radiogenomics Applied to Select Abdominal Tumors.

Invited Commentary: Radiogenomics Applied to Select Abdominal Tumors.

Decoding Genes: Current Update on Radiogenomics of Select Abdominal Malignancies.

Technologic advances in chromosomal analysis and DNA sequencing have enabled genome-wide analysis of cancer cells, yielding considerable data on the genetic basis of malignancies. Evolving knowledge of tumor genetics and oncologic pathways has led to a better understanding of histopathologic features, tumor classification, tumor biologic characteristics, and imaging findings and discovery of targeted therapeutic agents. Radiogenomics is a rapidly evolving field of imaging research aimed at correlating imaging features with gene mutations and gene expression patterns, and it may provide surrogate imaging biomarkers that may supplant genetic tests and be used to predict treatment response and prognosis and guide personalized treatment options. Multidetector CT, multiparametric MRI, and PET with use of multiple radiotracers are some of the imaging techniques commonly used to assess radiogenomic associations. Select abdominal malignancies demonstrate characteristic imaging features that correspond to gene mutations. Recent advances have enabled us to understand the genetics of steatotic and nonsteatotic hepatocellular adenomas, a plethora of morphologic-molecular subtypes of hepatic malignancies, a variety of clear cell and non-clear cell renal cell carcinomas, a myriad of hereditary and sporadic exocrine and neuroendocrine tumors of the pancreas, and the development of targeted therapeutic agents for gastrointestinal stromal tumors based on characteristic KIT gene mutations. Mutations associated with aggressive phenotypes of these malignancies can sometimes be predicted on the basis of their imaging characteristics. Radiologists should be familiar with the genetics and pathogenesis of common cancers that have associated imaging biomarkers, which can help them be integral members of the cancer management team and guide clinicians and pathologists. Online supplemental material is available for this article. ©RSNA, 2020 See discussion on this article by Luna (pp 1627-1630).

Spread through air spaces (STAS) in invasive mucinous adenocarcinoma of the lung: Incidence, prognostic impact, and prediction based on clinicoradiologic factors.

BackgroundSpread through air spaces (STAS) has recently been demonstrated to exhibit a negative impact on lung adenocarcinoma prognosis. However, most of these studies investigated STAS in nonmucinous adenocarcinoma. Here, we investigated the incidence of STAS in invasive mucinous adenocarcinoma (IMA) of the lung and evaluated whether tumor STAS was a risk factor of disease recurrence in IMA. We also examined clinicoradiologic factors in patients with IMA harboring STAS.MethodsWe reviewed pathologic specimens and imaging characteristics of primary tumors from 132 consecutive patients who underwent surgical resection for IMA to evaluate STAS. Patients with and without STAS were compared with respect to clinical characteristics as well as computed tomography (CT) imaging using logistic regression. The relationships between all variables including STAS and survival were analyzed.ResultsAmong a total of 132 patients, full pathologic specimens were available for 119 patients, and STAS was observed in 86 (72.3%). IMA patients with STAS were significantly associated with older age, presence of lobulated and spiculated margins on CT scan (P = 0.009, P = 0.006, and P = 0.027). In multivariate analysis for overall survival (OS), STAS was a borderline independent poor prognostic predictor (P = 0.028). Older age, history of smoking, higher T stage, presence of lymph node metastasis, and consolidative morphologic type remained independent predictors for OS.ConclusionsSTAS was associated with reduced OS and was a borderline independent poor prognostic factor in IMA. IMA with STAS was associated with older age and presence of lobulated and spiculated margins on CT scan.Key pointsSignificant findings of the studyCompared with other subtypes, IMA shows a higher incidence of STAS, which is an independent poor prognostic predictor even in IMA. Lobulated and spiculated margins on CT are associated with STAS.What this study addsConsidering that STAS can carry the potential for aerogenous metastasis, predicting STAS using preoperative surrogate CT imaging is desirable to avoid limited resection.