Study population and ethical protocol
This is a multi-center retrospective analysis of 3500 PCR-proved COVID-19 infection between March 2020 and December 2021. A cohort of 282 consecutive patients with COVID-19 vasculopathy was considered for inclusion.
Inclusion criteria were as follows: (1) Patients with a positive PCR test for Covid-19 infection, (2) Patients with available full clinical and laboratory records, and (3) Patients with routine chest CT and a positive imaging examination for COVID-19 vasculopathy.
Exclusion criteria were as follows: (1) Past history of vascular occlusion which necessitated seeking medical advice or primary vascular diseases such as vasculitis, (2) History of demyelinating diseases which may mimic the picture of neuro-vasculitis, (3) Incomplete medical records, and (4) Poor quality of images.
The Ethics Committee at the authors’ institution approved the study. On a retrospective basis, the Research Ethics Board waived the need for informed patient consent, stressing the assurance of the confidentiality of the patients' information and the medical records.
The patient cohort comprised 282 patients (204 males and 78 females, mean age 68 years ± 9 SD, age range 48–90 years).
A single expert consulting pulmonologist shared in this study with 21 years of experience in the field of pulmonology intensive care units.
The different imaging studies were analyzed in consensus by four expert consulting radiologists (14–33 years of experience) in addition to a senior resident.
Two types of MDCT scanners were utilized; the first is SOMATOM Sensation 64 (Siemens, Erlangen, Germany), while the other is Aquilion CXL/CX 128 (Toshiba, Canon Medical Systems, Tustin, CA, USA).
Two types of 1.5-Tesla MRI scanners were utilized; the first is GE Medical Systems, Sigma, USA, while the other is Magnotom ESPREE 1.5 T, Erlangen, Semines, Germany.
TOSHIBA Aplio 500 machine was utilized for Duplex assessment, using a transducer with frequency ranging from 5 to 13 MHz.
Routine chest CT analysis
The typical pulmonary CT findings for COVID-19 infection were assessed including ground-glass opacities (GGOs) and consolidations. Quantitative volumetric assessment for the pathological lung parenchyma was estimated by OsiriX MD 11.0 software after ROI 2D/3D reconstruction and threshold interval adjustment. An international volumetric CT severity scoring was utilized as follows: Score 1 corresponds to 0–25% lung involvement, Score 2 corresponds to 26–50%, Score 3 corresponds to 51–75%, and Score 4 corresponds to > 75% lung involvement .
Neurologic imaging analysis
Different imaging tools were included, as follows:
Non-enhanced CT for the brain was evaluated for diagnosis and localization of either non-hemorrhagic or hemorrhage ischemic infarctions as well as vasculitic areas.
CT-arteriography (CTA) of the cerebral circulations was utilized for diagnosis and localization of cerebrovascular arterial occlusion. It plays an important role for mapping prior to interventional procedures.
CT-perfusion (CTP) was utilized for delineation of the ischemic area as well as the cerebral blood flow and volume (CBF and CBV). A 60-s cine series was achieved at 0 to 5 s following injection of 40 ml of intra-venous non-ionic contrast at a 4–5 ml/s injection rate. CBV mapping was performed for the identification of hypo-perfused areas and the areas of the penumbra to predict patient prognosis and also as a base line examination before interventional procedure and follow up.
The conventional MRI sequences were utilized as follows: Axial and sagittal T1-WI, axial and coronal T2-WI, as well as FLAIR-WI. MRI examinations were requested by clinicians for either patients with unremarkable CT results such as in patients with vasculitis or patients with non-conclusive CT results as senile deep white matter lesions without definite CT signs of recent ischemia, or for confirmations of positive data in patients with small or subtle infarctions.
Diffusion-weighted image (DWI) MRI axial plane analysis was utilized. It is a T2-weighted, echo-planar spin-echo sequence EPI having MR-parameters as follows: TR = 3400 ms, TE = 100 ms, acquisition matrix = 192 × 192, slice thickness = 5 mm, gap = 0.3 mm with b value = 0, 500, 1000 s/mm2. The ADC value was measured in the ADC mapping inside the pathological area using a region of interest (ROI). Bright signal in the DWI in addition to low ADC value denotes positive diffusion restriction for recent ischemic infarctions.
Susceptibility weighted image (SWI) was utilized in addition to the conventional MRI sequences for detection of hemorrhagic transformation.
MR venography (MRV) was utilized via a time-of-flight (TOF) technique for the localization of venous sinus thrombosis. MRV examination were requested mainly in patients with infarctions along the water-shed zones especially when hemorrhagic.
MR arteriography (MRA) was utilized for mapping for large vascular occlusion prior to interventional procedures.
Pulmonary CTA analysis
The examination was performed in a caudo-cranial direction using a single breath-hold with full inspiration in a supine position. The following parameters were used: kVp = 120, mAs = 50–100, slice thickness = 1.25 mm, FOV = 350 × 350. A 50–60 ml of non-ionic IV was injected at a flow rate of 5.0–6.0 ml/s followed by a saline chaser. A bolus tracking was used at the threshold of 100 HU on the pulmonary trunk.
Three different greyscale windows were utilized as follows: (1) the lung window at 1500/−600, (2) the mediastinal window at 350/40, and (3) the pulmonary embolism window at 700/100. Minimal intensity projection (MIP) volume reconstruction was utilized for the assessment of vascular structures.
The CT signs of pulmonary vasculopathy were assessed as follows:
Acute pulmonary embolism is manifested by a central contrast filling defect.
Wedge-shaped sub-pleural pulmonary infarct.
Pulmonary vascular enlargement is manifested by abnormal pulmonary arterial dilatation inside and/or outside the pathological lung parenchyma with the loss of normal tapering .
The vascular ''tree-in-bud'' sign is manifested by the beaded appearance of peripheral pulmonary arterioles .
Gastro-intestinal CTA analysis
Urgent CTA examination, without special bowel preparation, was performed for assessment of the abdominal aorta and its major branches as well as the porto-mesenteric venous axis.
Patients with a clinical diagnosis of intestinal obstruction did not receive water oral intake or enema. On the other hand, patients with GIT bleeding received water enema without oral water intake because of severe vomiting.
Pre and post-contrast CT scans were performed. Post-contrast scans were obtained at the late arterial phase (45 s) and portal venous phases (70 s). Non-ionic 350 mol IV contrast medium was injected (1.5 ml/kg) at a flow rate of 3–4 ml/s.
Images were assessed using multi-planar reconstruction (MPR), curved planar reconstruction (CPR), and MIP.
The examined arteries and veins were traced for detection of any filling defect of thrombosis.
The small and large bowel were examined regarding the following: (1) Caliber: to diagnose and locate the site of obstruction, (2) Mural enhancement: to detect ischemic changes, (3) Submucosal edema (water halo sign), (4) Mural air (pneumatosis intestinal), (5) Surrounding fat stranding and (6) Loco-regional or distant free or loculated fluid collection.
Peripheral arterial analysis
Duplex studies were utilized for the detection of peripheral or central deep venous thrombosis. While CTA of the lower limbs was performed for detection of acute arterial occlusion. The patient was in a supine position with his feet entering the gantry first. The non-contrast phase was initially obtained followed by the post-contrast early arterial and late venous runoff phases. IV contrast dose was 1.5 ml/kg. The acquisition parameters were as follows: gantry rotation = 400 ms, collimation = 64 × 10 mm, mA = 80, kV = 120.
Mean, mode, median, variance, standard deviations, and ratios were calculated and compared. Chi-square and p value analysis was performed using an online calculator (http://www.alcula.com/calculators/statistics/). A p value < 0.05 was taken as a landmark for statistical significance. Additionally, a Pearson correlation coefficient (r) was utilized.