Longitudinal, Quantitative, Multimodal MRI Evaluation of Patients With Intracerebral Hemorrhage Over the First Year

In most patients with intracerebral hemorrhage (ICH), the hematoma and perihematomal area decrease over the subsequent months but patients continue to exhibit neurological impairments. In this serial imaging study, we characterized microstructural and neurophysiological changes in the ICH-affected brain tissues and collected the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Score (mRS), two clinical stroke scale scores. Twelve ICH patients were serially imaged on a 3T MRI at 1, 3, and 12 months (M) after injury. The hematoma and perihematomal volume masks were created and segmented using FLAIR imaging at 1 month which were applied to compute the susceptibilities (χ), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF) in the same tissues over time and in the matching contralesional tissues. At 3 M, there was a significant (p < 0.001) reduction in hematoma and perihematomal volumes. At 1 M, the χ, FA, and CBF were decreased in the perihematomal tissues as compared to the contralateral side, whereas MD increased. In the hematomal tissues, the χ increased whereas FA, MD, and CBF decreased as compared to the contralesional area at 1 M. Temporally, CBF in the hematoma and perihematomal tissues remained significantly (p < 0.05) lower compared with the contralesional areas whereas MD in the hematoma and χ in the perihematomal area increased. The NIHSS and mRS significantly correlated with hematoma and perihematomal volume but not with microstructural integrity. Our serial imaging studies provide new information on the long-term changes within the brain after ICH and our findings may have clinical significance that warrants future studies.

Dynamic right-to-left interatrial shunt may complicate severe COVID-19

Right-to-left (RTL) interatrial shunt (IAS) may complicate select cases of COVID-19 pneumonia. We describe the use of serial imaging to monitor shunt in critically ill patients. A 52-year-old man presented with COVID-19 pneumonia. Hypoxia worsened despite maximal medical therapy and non-invasive ventilation. On day 8, saline microbubble contrast-enhanced transthoracic echocardiography revealed a patent foramen ovale (PFO) with RTLIAS. Invasive ventilation was initiated the next day. The course was complicated by intermittent severe desaturation without worsening aeration or haemodynamic instability, so PFO closure was considered. However, on day 12, saline microbubble contrast-enhanced transoesophageal echocardiography excluded RTLIAS. The patient was extubated on day 27 and discharged home 12 days later. Thus, RTLIAS may be dynamic and changes can be detected and monitored by serial imaging. Bedside echocardiography with saline microbubble contrast, a simple, minimally invasive bedside test, may be useful in the management of patients with severe hypoxia.

Early Imaging and Molecular Changes with Neoadjuvant Bevacizumab in Stage II/III Breast Cancer

This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2–C5). Tumour proliferation and hypoxic status were evaluated using 18F-fluoro-3′-deoxy-3′-L-fluorothymidine (FLT)- and 18F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre- and post-bevacizumab vascular changes were evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p ≤ 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques and molecular gene profiling identified several potentially predictive biomarkers that may predict response to neoadjuvant bevacizumab therapy in BC patients.

Serial imaging of micro-agents and cancer cell spheroids in a microfluidic channel using multicolor fluorescence microscopy

Multicolor fluorescence microscopy is a powerful technique to fully visualize many biological phenomena by acquiring images from different spectrum channels. This study expands the scope of multicolor fluorescence microscopy by serial imaging of polystyrene micro-beads as surrogates for drug carriers, cancer spheroids formed using HeLa cells, and microfluidic channels. Three fluorophores with different spectral characteristics are utilized to perform multicolor microscopy. According to the spectrum analysis of the fluorophores, a multicolor widefield fluorescence microscope is developed. Spectral crosstalk is corrected by exciting the fluorophores in a round-robin manner and synchronous emitted light collection. To report the performance of the multicolor microscopy, a simplified 3D tumor model is created by placing beads and spheroids inside a channel filled with the cell culture medium is imaged at varying exposure times. As a representative case and a method for bio-hybrid drug carrier fabrication, a spheroid surface is coated with beads in a channel utilizing electrostatic forces under the guidance of multicolor microscopy. Our experiments show that multicolor fluorescence microscopy enables crosstalk-free and spectrally-different individual image acquisition of beads, spheroids, and channels with the minimum exposure time of 5.5 ms. The imaging technique has the potential to monitor drug carrier transportation to cancer cells in real-time.

Investigating the effect of micro-CT radiation dose on tumour growth in mice

Micro-CT systems are used to obtain high-resolution CT images of small animals in vivo. The physical principals of x-ray CT require that the radiation dose delivered to the subject increase rapidly to achieve finer resolution while maintaining image quality. The effect of micro-CT imaging dose on tumour growth in mice was investigated in longitudinal imaging study. Four groups of tumour bearing mice were used: a control group that received no radiation, and three unique imaging groups that received low, medium and high dose scans respectively. The mice underwent their imaging protocols four times, once every four days starting the fourth day post inoculation. The results of an ANOVA test indicate the serial imaging did not cause a statistically significant difference in tumour growth among the four groups. The notion that serial imaging causes an effect equivalent to radiotherapy treatment can confidently be rejected (α + 0.1, β = 0.1).

Investigating the effect of micro-CT radiation dose on tumour growth in mice

Micro-CT systems are used to obtain high-resolution CT images of small animals in vivo. The physical principals of x-ray CT require that the radiation dose delivered to the subject increase rapidly to achieve finer resolution while maintaining image quality. The effect of micro-CT imaging dose on tumour growth in mice was investigated in longitudinal imaging study. Four groups of tumour bearing mice were used: a control group that received no radiation, and three unique imaging groups that received low, medium and high dose scans respectively. The mice underwent their imaging protocols four times, once every four days starting the fourth day post inoculation. The results of an ANOVA test indicate the serial imaging did not cause a statistically significant difference in tumour growth among the four groups. The notion that serial imaging causes an effect equivalent to radiotherapy treatment can confidently be rejected (α + 0.1, β = 0.1).

Cardiac magnetic resonance in COVID-19 positive and probable cases: A report from a high volume CMR centre in Ireland

Funding Acknowledgements Type of funding sources: None. Introduction Coronavirus disease 2019 (COVID-19) infection can have multisystem involvements. The inflammation sequelae can cause myocarditis. The COVID-19 pandemic has impacted Ireland significantly. Understanding of myocardial involvement in COVID-19 is not fully elucidated but has been reported. The Centre for Cardiovascular Magnetic Resonance, Blackrock Clinic in Ireland is a high volume CMR centre with approximately 4500 cases per year and accepting referral from all hospital in Ireland. These analyses are to describe the CMR findings in COVID-19 positive and probable cases attending the centre. Methods Consecutive 65 referrals with mention of "COVID-19" from March 2020 to December 2020 was assessed. 56 cases were included in this analysis. Cases were categorised as COVID-19 positive cases or probable (viral illness like symptoms) cases. The demography and CMR parameters were collected. Serial imaging of selected cases was included. Descriptive analyses methods were applied. Results In the period of 10 months, there was 49 COVID-19 positive cases (65.3% male; median age 49 [32 : 61] years) and 7 COVID-19 probable cases (42.9% male; median age 39 [37 : 59] years). In the COVID-19 positive cases, 25 had normal CMR, 11 has evidence of myocarditis, 1 with pericarditis, 2 with infarction/ischaemia, 3 with dilated cardiomyopathy, 2 with hypertrophic cardiomyopathy and 5 with other findings. There were 3 COVID-19 positive cases with serial imaging showing resolving myocarditis (100% female; median age 41 [30 : 47] years). 2 professional athletes with COVID-19 positive test showed no evidence of myocarditis. There are no significant differences in the age of male COVID-19 positive versus female group (p= 0.0752). Different demography and CMR parameters and tissue characterisation are described in Table 1 and Table 2. Conclusions The prevalence of myocarditis in this cohort is approximately 1 in 5 (21.4%). Within the COVID-19 positive cases, the prevalence is 22.4%. These observations may reflect selection bias for CMR referral in those with cardiac symptoms or cardiac enzymes leak.