Chest CT Patterns from Diagnosis to 1 Year of Follow-up in Patients with COVID-19.

Background The chest CT manifestations of COVID-19 from hospitalization to convalescence after 1 year are unknown. Purpose To assess chest CT manifestations of COVID-19 up to 1 year after symptom onset. Materials and Methods Patients were enrolled if they were admitted to the hospital because of COVID-19 and underwent CT during hospitalization at two isolation centers between January 27, 2020, and March 31, 2020. In a prospective study, three serial chest CT scans were obtained at approximately 3, 7, and 12 months after symptom onset and were longitudinally analyzed. The total CT score of pulmonary lobe involvement, ranging from 0 to 25, was assessed (score of 1-5 for each lobe). Univariable and multivariable logistic regression analyses were performed to explore independent risk factors for residual CT abnormalities after 1 year. Results A total of 209 study participants (mean age, 49 years ± 13 [standard deviation]; 116 women) were evaluated. CT abnormalities had resolved in 61% of participants (128 of 209) at 3 months and in 75% of participants (156 of 209) at 12 months. Among participants with chest CT abnormalities that had not resolved, there were residual linear opacities in 25 of the 209 participants (12%) and multifocal reticular or cystic lesions in 28 of the 209 participants (13%). Age 50 years or older, lymphopenia, and severe or aggravation of acute respiratory distress syndrome were independent risk factors for residual CT abnormalities at 1 year (odds ratios = 15.9, 18.9, and 43.9, respectively; P < .001 for each comparison). In 53 participants with residual CT abnormalities at 12 months, reticular lesions (41 of 53 participants [77%]) and bronchial dilation (39 of 53 participants [74%]) were observed at discharge and were persistent in 28 (53%) and 24 (45%) of the 53 participants, respectively. Conclusion One year after COVID-19 diagnosis, chest CT scans showed abnormal findings in 53 of the 209 study participants (25%), with 28 of the 209 participants (13%) showing subpleural reticular or cystic lesions. Older participants with severe COVID-19 or acute respiratory distress syndrome were more likely to develop lung sequelae that persisted at 1 year. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lee and Wi et al in this issue.

Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19).

Background Chest CT is used to assess the severity of lung involvement in coronavirus disease 2019 (COVID-19). Purpose To determine the changes in chest CT findings associated with COVID-19 from initial diagnosis until patient recovery. Materials and Methods This retrospective review included patients with real-time polymerase chain reaction-confirmed COVID-19 who presented between January 12, 2020, and February 6, 2020. Patients with severe respiratory distress and/or oxygen requirement at any time during the disease course were excluded. Repeat chest CT was performed at approximately 4-day intervals. Each of the five lung lobes was visually scored on a scale of 0 to 5, with 0 indicating no involvement and 5 indicating more than 75% involvement. The total CT score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). Results Twenty-one patients (six men and 15 women aged 25-63 years) with confirmed COVID-19 were evaluated. A total of 82 chest CT scans were obtained in these patients, with a mean interval (±standard deviation) of 4 days ± 1 (range, 1-8 days). All patients were discharged after a mean hospitalization period of 17 days ± 4 (range, 11-26 days). Maximum lung involved peaked at approximately 10 days (with a calculated total CT score of 6) from the onset of initial symptoms (R2 = 0.25, P < .001). Based on quartiles of chest CT scans from day 0 to day 26 involvement, four stages of lung CT findings were defined. CT scans obtained in stage 1 (0-4 days) showed ground-glass opacities (18 of 24 scans [75%]), with a mean total CT score of 2 ± 2; scans obtained in stage 2 (5-8 days) showed an increase in both the crazy-paving pattern (nine of 17 scans [53%]) and total CT score (mean, 6 ± 4; P = .002); scans obtained in stage 3 (9-13 days) showed consolidation (19 of 21 scans [91%]) and a peak in the total CT score (mean, 7 ± 4); and scans obtained in stage 4 (≥14 days) showed gradual resolution of consolidation (15 of 20 scans [75%]) and a decrease in the total CT score (mean, 6 ± 4) without crazy-paving pattern. Conclusion In patients recovering from coronavirus disease 2019 (without severe respiratory distress during the disease course), lung abnormalities on chest CT scans showed greatest severity approximately 10 days after initial onset of symptoms. © RSNA, 2020.

Dynamic 1 H imaging of hyperpolarized [1-13 C]lactate in vivo using a reverse INEPT experiment.

PURPOSE: Dynamic magnetic resonance spectroscopic imaging of hyperpolarized 13 C-labeled cell substrates has enabled the investigation of tissue metabolism in vivo. Currently observation of these hyperpolarized substrates is limited mainly to 13 C detection. We describe here an imaging pulse sequence that enables proton observation by using polarization transfer from the hyperpolarized 13 C nucleus to spin-coupled protons. METHODS: The pulse sequence transfers 13 C hyperpolarization to 1 H using a modified reverse insensitive nuclei enhanced by polarization transfer (INEPT) sequence that acquires a fully refocused echo. The resulting hyperpolarized 1 H signal is acquired using a 2D echo-planar trajectory. The efficiency of polarization transfer was investigated using simulations with and without T1 and T2 relaxation of both the 1 H and 13 C nuclei. RESULTS: Simulations showed that 1 H detection of the hyperpolarized 13 C nucleus in lactate should increase significantly the signal-to-noise ratio when compared with direct 13 C detection at 3T. However the advantage of 1 H detection is expected to disappear at higher fields. Dynamic 1 H images of hyperpolarized [1-13 C]lactate, with a spatial resolution of 1.25 × 1.25 mm2 , were acquired from a phantom injected with hyperpolarized [1-13 C]lactate and from tumors in vivo following injection of hyperpolarized [1-13 C]pyruvate. CONCLUSIONS: The sequence allows 1 H imaging of hyperpolarized 13 C-labeled substrates in vivo. Magn Reson Med 79:741-747, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Hyperpolarized 13 C spectroscopic imaging using single-shot 3D sequences with unpaired adiabatic refocusing pulses.

Hyperpolarized MRI with 13 C-labeled metabolites has enabled metabolic imaging of tumors in vivo. The heterogeneous nature of tumors and the limited lifetime of the hyperpolarization require high resolution, both temporally and spatially. We describe two sequences that make more efficient use of the 13 C polarization than previously described single-shot 3D sequences. With these sequences, the target metabolite resonances were excited using spectral-spatial pulses and the data acquired using spiral readouts from a series of echoes created using a fast-spin-echo sequence employing adiabatic 180° pulses. The third dimension was encoded with blipped gradients applied in an interleaved order to the echo train. Adiabatic inversion pulses applied in the absence of slice selection gradients allowed acquisition of signal from odd echoes, formed by unpaired adiabatic pulses, as well as from even echoes. The sequences were tested on tumor-bearing mice following intravenous injection of hyperpolarized [1-13 C]pyruvate. [1-13 C] pyruvate and [1-13 C] lactate images were acquired in vivo with a 4 × 4 × 2 cm3 field of view and a 32 × 32 × 16 matrix, leading to a nominal resolution of 1.25 × 1.25 × 1.25 mm3 and an effective resolution of 1.25 × 1.25 × 4.5 mm3 when the z-direction point spread function was taken into account. The acquisition of signal from more echoes also allowed for an improvement in the signal-to-noise ratio for resonances with longer T2 relaxation times. The pulse sequences described here produced hyperpolarized 13 C images with improved resolution and signal-to-noise ratio when compared with similar sequences described previously.

A referenceless Nyquist ghost correction workflow for echo planar imaging of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate.

Single-shot echo planar imaging (EPI), which allows an image to be acquired using a single excitation pulse, is used widely for imaging the metabolism of hyperpolarized 13 C-labelled metabolites in vivo as the technique is rapid and minimizes the depletion of the hyperpolarized signal. However, EPI suffers from Nyquist ghosting, which normally is corrected for by acquiring a reference scan. In a dynamic acquisition of a series of images, this results in the sacrifice of a time point if the reference scan involves a full readout train with no phase encoding. This time penalty is negligible if an integrated navigator echo is used, but at the cost of a lower signal-to-noise ratio (SNR) as a result of prolonged T2 * decay. We describe here a workflow for hyperpolarized 13 C EPI that requires no reference scan. This involves the selection of a ghost-containing background from a 13 C image of a single metabolite at a single time point, the identification of phase correction coefficients that minimize signal in the selected area, and the application of these coefficients to images acquired at all time points and from all metabolites. The workflow was compared in phantom experiments with phase correction using a 13 C reference scan, and yielded similar results in situations with a regular field of view (FOV), a restricted FOV and where there were multiple signal sources. When compared with alternative phase correction methods, the workflow showed an SNR benefit relative to integrated 13 C reference echoes (>15%) or better ghost removal relative to a 1 H reference scan. The residual ghosting in a slightly de-shimmed B0 field was 1.6% using the proposed workflow and 3.8% using a 1 H reference scan. The workflow was implemented with a series of dynamically acquired hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate images in vivo, resulting in images with no observable ghosting and which were quantitatively similar to images corrected using a 13 C reference scan.

Pelvic congestion syndrome: etiology of pain, diagnosis, and clinical management.

Pelvic congestion syndrome is associated with pelvic varicosities that result in chronic pelvic pain, especially in the setting of prolonged standing, coitus, menstruation, and pregnancy. Although the underlying pathophysiology of pelvic congestion syndrome is unclear, it probably results from a combination of dysfunctional venous valves, retrograde blood flow, venous hypertension, and dilatation. Asymptomatic women may also have pelvic varicosities, making pelvic congestion syndrome difficult to diagnose. This article explores the etiologies of pain, use of imaging techniques, and clinical management of pelvic congestion syndrome. Possible explanations for the spectrum of pain among women with pelvic varicosities are also discussed.

May-Thurner syndrome: diagnosis and management.

For over fifty years, the pathogenesis of May-Thurner syndrome (MTS) has been associated with chronic left common iliac vein compression resulting in the formation of intraluminal, permanent obstructive lesions. However, despite this association, the mechanism by which compression produces these lesions is unknown. Diagnostic accuracy of MTS is critical since it often afflicts young patients requiring endovascular management. This review will focus on the historical, embryological and evolutionary description of MTS and examine its development, diagnosis, clinical management and potential diagnostic errors.

Acute appendicitis and retroperitoneal abscess: rare complications of sigmoid diverticulitis.

Diverticulitis is a common cause of an acute surgical abdomen and computed tomography has become an essential part of work up particularly to identify complications that commonly include intraperitoneal perforation, abscess and fistula formation. We report the case of an 81-year-old male who presented to the emergency department with acute lower abdominal pain and was found to have sigmoid diverticulitis with the rare complications of a diverticular abscess that had formed a sinus tract and perforated into the retroperitoneum and secondary acute appendicitis. Initial management was with intravenous antibiotics, a Hartmann's procedure and appendicectomy. Subsequently the retroperitoneal collection was drained percutaneously. The case was further complicated by the patient's multiple co-morbidities and unfortunately the patient died 6 weeks after admission from sepsis. This case highlights the role of computed tomography in the pre- and post-operative period to identify complications which are often clinically occult and require early surgical and interventional radiology management to optimize outcomes.

An adaptable two-color flow cytometric assay to quantitate the invasion of erythrocytes by Plasmodium falciparum parasites.

Plasmodium falciparum genotyping has recently undergone a revolution, and genome-wide genotype datasets are now being collected for large numbers of parasite isolates. By contrast, phenotyping technologies have lagged behind, with few high throughput phenotyping platforms available. Invasion of human erythrocytes by Plasmodium falciparum is a phenotype of particular interest because of its central role in parasite development. Invasion is a variable phenotype influenced by natural genetic variation in both the parasite and host and is governed by multiple overlapping and in some instances redundant parasite-erythrocyte interactions. To facilitate the scale-up of erythrocyte invasion phenotyping, we have developed a novel platform based on two-color flow cytometry that distinguishes parasite invasion from parasite growth. Target cells that had one or more receptors removed using enzymatic treatment were prelabeled with intracellular dyes CFDA-SE or DDAO-SE, incubated with P. falciparum parasites, and parasites that had invaded either labeled or unlabeled cells were detected with fluorescent DNA-intercalating dyes Hoechst 33342 or SYBR Green I. Neither cell label interfered with erythrocyte invasion, and the combination of cell and parasite dyes recapitulated known invasion phenotypes for three standard laboratory strains. Three different dye combinations with minimal overlap have been validated, meaning the same assay can be adapted to instruments harboring several different combinations of laser lines. The assay is sensitive, operates in a 96-well format, and can be used to quantitate the impact of natural or experimental genetic variation on erythrocyte invasion efficiency.

Different computed tomography patterns of Coronavirus Disease 2019 (COVID-19) between survivors and non-survivors.

This study aimed to compare the chest computed tomography (CT) findings between survivors and non-survivors with Coronavirus Disease 2019 (COVID-19). Between 12 January 2020 and 20 February 2020, the records of 124 consecutive patients diagnosed with COVID-19 were retrospectively reviewed and divided into survivor (83/124) and non-survivor (41/124) groups. Chest CT findings were qualitatively compared on admission and serial chest CT scans were semi-quantitively evaluated between two groups using curve estimations. On admission, significantly more bilateral (97.6% vs. 73.5%, p = 0.001) and diffuse lesions (39.0% vs. 8.4%, p < 0.001) with higher total CT score (median 10 vs. 4, p < 0.001) were observed in non-survivor group compared with survivor group. Besides, crazy-paving pattern was more predominant in non-survivor group than survivor group (39.0% vs. 12.0%, p < 0.001). From the prediction of curve estimation, in survivor group total CT score increased in the first 20 days reaching a peak of 6 points and then gradually decreased for more than other 40 days (R2 = 0.545, p < 0.001). In non-survivor group, total CT score rapidly increased over 10 points in the first 10 days and gradually increased afterwards until ARDS occurred with following death events (R2 = 0.711, p < 0.001). In conclusion, persistent progression with predominant crazy-paving pattern was the major manifestation of COVID-19 in non-survivors. Understanding this CT feature could help the clinical physician to predict the prognosis of the patients.

Metabolic Imaging Detects Resistance to PI3Kα Inhibition Mediated by Persistent FOXM1 Expression in ER+ Breast Cancer.

PIK3CA, encoding the PI3Kα isoform, is the most frequently mutated oncogene in estrogen receptor (ER)-positive breast cancer. Isoform-selective PI3K inhibitors are used clinically but intrinsic and acquired resistance limits their utility. Improved selection of patients that will benefit from these drugs requires predictive biomarkers. We show here that persistent FOXM1 expression following drug treatment is a biomarker of resistance to PI3Kα inhibition in ER+ breast cancer. FOXM1 drives expression of lactate dehydrogenase (LDH) but not hexokinase 2 (HK-II). The downstream metabolic changes can therefore be detected using MRI of LDH-catalyzed hyperpolarized 13C label exchange between pyruvate and lactate but not by positron emission tomography measurements of HK-II-mediated trapping of the glucose analog 2-deoxy-2-[18F]fluorodeoxyglucose. Rapid assessment of treatment response in breast cancer using this imaging method could help identify patients that benefit from PI3Kα inhibition and design drug combinations to counteract the emergence of resistance.

Emerging Functional Imaging Biomarkers of Tumour Responses to Radiotherapy.

Tumour responses to radiotherapy are currently primarily assessed by changes in size. Imaging permits non-invasive, whole-body assessment of tumour burden and guides treatment options for most tumours. However, in most tumours, changes in size are slow to manifest and can sometimes be difficult to interpret or misleading, potentially leading to prolonged durations of ineffective treatment and delays in changing therapy. Functional imaging techniques that monitor biological processes have the potential to detect tumour responses to treatment earlier and refine treatment options based on tumour biology rather than solely on size and staging. By considering the biological effects of radiotherapy, this review focusses on emerging functional imaging techniques with the potential to augment morphological imaging and serve as biomarkers of early response to radiotherapy.

Magnetic Resonance Imaging Is More Sensitive Than PET for Detecting Treatment-Induced Cell Death-Dependent Changes in Glycolysis.

Metabolic imaging has been widely used to measure the early responses of tumors to treatment. Here, we assess the abilities of PET measurement of [18F]FDG uptake and MRI measurement of hyperpolarized [1-13C]pyruvate metabolism to detect early changes in glycolysis following treatment-induced cell death in human colorectal (Colo205) and breast adenocarcinoma (MDA-MB-231) xenografts in mice. A TRAIL agonist that binds to human but not mouse cells induced tumor-selective cell death. Tumor glycolysis was assessed by injecting [1,6-13C2]glucose and measuring 13C-labeled metabolites in tumor extracts. Injection of hyperpolarized [1-13C]pyruvate induced rapid reduction in lactate labeling. This decrease, which correlated with an increase in histologic markers of cell death and preceded decrease in tumor volume, reflected reduced flux from glucose to lactate and decreased lactate concentration. However, [18F]FDG uptake and phosphorylation were maintained following treatment, which has been attributed previously to increased [18F]FDG uptake by infiltrating immune cells. Quantification of [18F]FDG uptake in flow-sorted tumor and immune cells from disaggregated tumors identified CD11b+/CD45+ macrophages as the most [18F]FDG-avid cell type present, yet they represented <5% of the cells present in the tumors and could not explain the failure of [18F]FDG-PET to detect treatment response. MRI measurement of hyperpolarized [1-13C]pyruvate metabolism is therefore a more sensitive marker of the early decreases in glycolytic flux that occur following cell death than PET measurements of [18F]FDG uptake. SIGNIFICANCE: These findings demonstrate superior sensitivity of MRI measurement of hyperpolarized [1-13C]pyruvate metabolism versus PET measurement of 18F-FDG uptake for detecting early changes in glycolysis following treatment-induced tumor cell death.

Magnetic resonance imaging of cancer metabolism with hyperpolarized 13C-labeled cell metabolites.

Hyperpolarization of 13C-labeled substrates can increase their 13C NMR signal by more than 10000-fold, which has allowed magnetic resonance imaging (MRI) of metabolic reactions in vivo. This has already provided a unique insight into the dysregulated metabolic pathways and microenvironment of tumors. Perhaps the best known of the cancer-associated metabolic aberrations is the Warburg effect, which has been imaged in patients using hyperpolarized [1-13C]pyruvate. In clinical oncology there is a requirement to diagnose tumors earlier, better determine their aggressiveness and prognosis, identify novel treatment targets and detect response to treatment earlier. Here we consider some of the hyperpolarized substrates that have been developed and have the potential to meet these requirements and become the precision imaging tools of the future.

Glyoxalase activity in human erythrocytes and mouse lymphoma, liver and brain probed with hyperpolarized 13C-methylglyoxal.

Methylglyoxal is a faulty metabolite. It is a ubiquitous by-product of glucose and amino acid metabolism that spontaneously reacts with proximal amino groups in proteins and nucleic acids, leading to impairment of their function. The glyoxalase pathway evolved early in phylogeny to bring about rapid catabolism of methylglyoxal, and an understanding of the role of methylglyoxal and the glyoxalases in many diseases is beginning to emerge. Metabolic processing of methylglyoxal is very rapid in vivo and thus notoriously difficult to detect and quantify. Here we show that 13C nuclei in labeled methylglyoxal can be hyperpolarized using dynamic nuclear polarization, providing 13C nuclear magnetic resonance signal enhancements in the solution state close to 5,000-fold. We demonstrate the applications of this probe of metabolism for kinetic characterization of the glyoxalase system in isolated cells as well as mouse brain, liver and lymphoma in vivo.

Radiomics and circulating tumor cells: personalized care in hepatocellular carcinoma?

Personalized care in oncology is expected to significantly improve morbidity and mortality, facilitated by our increasing understanding of the molecular mechanisms driving tumors and the ability to target those drivers. Hepatocellular carcinoma has a very high mortality to incidence ratio despite localized disease being curable, emphasizing the importance of early diagnosis. Radiomics, the use of imaging technology to extrapolate molecular tumor data, and the detection of circulating tumor cells (CTCs) are two new technologies that could be incorporated into the clinical setting with relative ease. Here we discuss the molecular mechanisms leading to the development of hepatocellular carcinoma focusing on the latest developments in liver magnetic resonance imaging, CTC, and radiomic technology and their potential to improve diagnosis, staging, and therapy.

Hepatocellular carcinoma: can circulating tumor cells and radiogenomics deliver personalized care?

The 'omics revolution is facilitating a personalized approach to improving outcome by refining diagnosis, staging, treatment, and monitoring of hepatocellular carcinoma. Furthermore, the promise of being able to target a range of specific tumor drivers at a molecular level offers exciting new therapy prospects for a disease that is notoriously difficult to treat. We provide a unique perspective combining our understanding of the molecular mechanisms of hepatocellular carcinoma development with the potential of circulating tumor cells and radiogenomics to change the drivers of decision-making used in current practice.