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19th December 2022
The identification of enlarged perivascular spaces in the centrum semiovale in patients with migraine compared to healthy controls, is suggestive of a disruption in the glymphatic system according to the findings of a study using ultra-high-field 7T MRI and presented at the Radiological Society of North America conference 2022.
Migraine is a common headache-related condition that affects an estimated 12% of the population. With the development of magnetic resonance imaging, it has become clear that some migraine patients (both with and without aura) are at an increased risk for subclinical lesions in certain brain areas. Such lesions include white matter hyper-intensities (WMH), i.e., lesions that have infarction features but which do not cause any clinical symptoms or other stroke-related signs. In addition, cerebral micro-bleeds (CMBs) are another biomarker of small-vessel disease and which have been found to co-occur with infarcts more often in migraine than in control patients. Advances in imaging techniques by 7 Tesla MRI might improve the visualisation of smaller anatomical structures and allow detailed pathological findings with a high spatial resolution by reducing the voxel size related to the increased signal-to-noise (SNR) ratio.
In the present study, US researchers used the 7T MRI modality to study microvascular changes in the brain due to migraine, particularly in perivascular spaces and compared the findings with those seen in headache-free control patients. They enrolled participants with both chronic migraine (CM), episodic migraine without aura (EMWoA) and age matched healthy controls. Patients were excluded if they had overt cognitive impairment, a brain tumour, prior intracranial surgery, contraindications to MRI or if they suffered with claustrophobia. The team calculated enlarged perivascular volume spaces (EPVS) in the centrum semiovale (CSO) and basal ganglia (BG), WMH using the Fazekas scale, and CMB using the micro-bleed anatomical rating scale. In addition, they also collected clinical data such as disease duration and severity, symptoms at time of scan, presence of aura, and side of headache.
Enlarged perivascular spaces in migraine and control patients
A total of 10 CM, 10 EMWoA and 5 health control participants were included.
The results showed that the number of EPVS in the CSO, but not in the BG, was significantly higher with migraine compared to healthy controls (p = 0.04). However, while the frequency of WMH and CMB in migraine did not significantly differ from controls, among migraine patients, there was a significant correlation between EPVS quantity in CSO and deep WMH severity (p = 0.04).
The authors concluded that there were significant differences in the EPVS in migraine compared to controls and which might indicate be suggestive of glymphatic disruption, i.e., the system for clearance of waste materials from the central nervous system and which utilises perivascular channels. Nevertheless, whether such changes affect migraine development or result from migraine is unknown.
In a related press release, study co-author Wilson Xu, from Keck School of Medicine of the University of Southern California in Los Angeles, said ‘although we didn’t find any significant changes in the severity of white matter lesions in patients with and without migraine, these white matter lesions were significantly linked to the presence of enlarged perivascular spaces. He added how ‘this suggests that changes in perivascular spaces could lead to future development of more white matter lesions.’
Citation
Xu W et al. Migraine-Associated Vascular Changes on Structural 7T-MRI. RSNA 2022
16th December 2022
Non-steroidal anti-inflammatory drugs (NSAIDs) used for the management of osteoarthritis appear to worsen inflammation in the knee joint over time, according to a study presented at the Radiological Society of North America (RSNA) conference 2022.
NSAIDs such as ibuprofen and naproxen are widely recommended and prescribed to treat pain in osteoarthritis yet are also known to elicit adverse events affecting the gastrointestinal, cardiovascular, and renal systems. In fact, one US study of patients with knee osteoarthritis (OA) revealed how non-prescription non-steroidal anti-inflammatory drugs were the most frequently reported medications (26.8%), even in those more than 75-years old. In recent years attention has focused on the role of the synovium in OA and how the presence of synovitis is associated with more severe pain and joint dysfunction and may be predictive of faster rates of cartilage loss in certain patient populations. However, whether NSAIDs are beneficial to patients with OA in the longer term remains uncertain, though some data suggests that there may not be long-term benefits given how a majority of patients had persistent pain and disability despite therapy.
In the study presented at RSNA, researchers set out to analyse the association between NSAID use and synovitis in patients with osteoarthritis of the knee and to assess how treatment with NSAIDs affects joint structure over time. The team used data derived from participants from the Osteoarthritis Initiative (OAI) cohort who had moderate to severe OA and sustained NSAID treatment for at least 12 months between baseline and 4-year follow-up. The outcomes for these participants were then compared with non-NSAID treated participants. All participants underwent a 3T MRI of the knee at baseline and after 4 years. and images were semi-quantitatively scored for MR biomarkers of synovial inflammation (effusion-synovitis, size and signal intensity of infra-patellar fat pad (IFP) and the synovial proliferation score (SPS). Cartilage thickness and T2-relaxation time measurements served as non-invasive biomarkers for evaluating OA progression. The associations between baseline and findings after 4 years were investigated with linear regression models (including adjustment for sex, BMI, age, pain, K/L grade).
NSAIDs and arthritic markers over time
A total of 721 participants (129 with and 592 participants without regular usage of NSAID) were included in the analysis. At baseline, there was a significantly higher signal intensity in the IFP among NSAID users as compared to controls (adjusted difference in score = 0.26, 95% CI -0.5 – 0.129, p = 0.039). Additionally, when assessed over time, there was a significantly higher increase in the signal intensity of IFP (0.46, 95% CI 0.2 – 0.72, p < 0.001) and a higher increase in effusion synovitis (0.27, 95% CI 0.06 – 0.47, p = 0.01) in NSAID users compared to controls. The size of IFP and SPS did not show a significant difference between groups at baseline and no significant change over time. NSAID users showed more degenerative changes regarding T2-relaxation time and cartilage thickness over time, but this did not reach statistical significance.
Based on these findings, the authors suggested that among those using NSAIDs, there was a higher signal intensity in IFP and more effusion/ synovitis than controls, indicating that long-term NSAID usage is associated with more synovitis.
Commenting on these findings in a press release, lead author, Johanna Luitjens, a postdoctoral scholar in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco, said ‘in this large group of participants, we were able to show that there were no protective mechanisms from NSAIDs in reducing inflammation or slowing down progression of osteoarthritis of the knee joint.’ She added that ‘the anti-inflammatory effect that normally comes from NSAIDs may not effectively prevent synovitis, with progressive degenerative change resulting in worsening of synovitis over time.’
Citation
Luitjens J et al. Impact of Non-steroidal Anti-inflammatory Drugs (NSAIDs) on Synovitis and the Progression of Osteoarthritis: Data from the Osteoarthritis Initiative (OAI). RSNA conference 2022.
21st November 2022
A prostate cancer screening strategy that involves an MRI scan following a prostate specific antigen (PSA) test with subsequent targeted biopsies, is a more cost-effective strategy than using just a PSA and standard biopsy according to a cost-effectiveness analysis by Swedish researchers.
Prostate cancer (PCa) screening based on PSA, has been shown in a 16-year follow-up study, to reduce prostate cancer mortality. A biopsy is normally used to confirm the diagnosis of PCa though in recent years there has been an increase in the role of magnetic resonance imaging (MRI) as an alternative means for the identification of PCa. In fact, data suggests that the use of multi-parametric magnetic resonance imaging (MP-MRI) might allow 27% of patients to avoid a primary biopsy. In a 2021 study which compared MRI-targeted or standard biopsy for the purposes of screening for PCa, it was found that in men with a PSA level > 3 ng/ml, an MRI result suggestive of prostate cancer was non-inferior to standard biopsy for detecting clinically significant prostate cancer. In the trial, men were randomised to either a 10 to 12-core standard biopsy or to undergo a triage MRI and then a standard biopsy if the MRI results suggested prostate cancer. Given the non-inferior findings of this study, the Swedish team set out to determine the cost-effectiveness of the MRI-based screening approach in men aged 55 to 69 years of age.
The researchers modelled three scenarios: no screening (strategy 1); PSA and standard biopsy every four years (strategy 2) and finally, MRI following an elevated PSA and then a standard biopsy if the men had a PI-RADS value of between 3 and 5, i.e., which is suggestive of PCa. For each of the three strategies, the team modelled several different outcomes including the mean lifetime number of screening tests, MRIs, over-diagnosis (where screening was positive but would not have presented with symptoms before death due to other causes) and deaths. The incremental cost-effectiveness ratio (ICER), which represents the additional cost of one unit of outcome gained by one strategy compared with another, was calculated for each scenario. The ICER was calculated by dividing the difference in costs by the difference in quality-adjusted life-years (QALYs) for the no screening and the two alternative strategies.
Prostate cancer screening and cost-effectiveness
A total of 603 men were randomised to the standard arm and 929 to the MRI arm and of whom, 11.9% underwent MRI or any biopsy.
When compared against a strategy of no screening, the ICER for the MRI and combined biopsies was $53,736 per QALY gained compared to $69,254 for the PSA and standard biopsy strategy and which the authors designated as a moderate cost per QALY gain. Furthermore, MRI-based screening reduced the number of lifetime biopsies and over-diagnosis by approximately 50% and had a high probability of being cost-effective compared to the alternative strategies.
The authors concluded that a strategy for prostate cancer screening based on PSA followed by MRI with subsequent combined targeted and standard biopsies, had a high probability to be more cost-effective compared with the traditional screening pathway using PSA and a standard biopsy.
Citation
Hao S et al. Cost-effectiveness of Prostate Cancer Screening Using Magnetic Resonance Imaging or Standard Biopsy Based on the STHLM3-MRI Study. JAMA Oncol 2022
24th August 2022
A machine-learning MRI model is better able to predict the recurrence of hepatocellular carcinoma (HCC) after a liver transplant than a model based on clinical and laboratory data but is equally effective to a model which uses a combination of clinical/laboratory and MRI-derived data according to a study by US and German researchers.
Liver cancer, of which HCC accounts for about 90% of all cases, remains a global health challenge and it is estimated to have an incidence of over a million cases by 2025. Potentially curative treatment options for hepatocellular carcinoma include liver transplantation, liver resection and thermal ablation, with transplantation offering the lowest rate of cancer recurrence and highest chance of long-term survival.
However, despite this, estimated post-transplantation recurrence rates are between 15% and 20%. Methods to estimate the risk of recurrence are therefore needed and hepatobiliary magnetic resonance imaging (MRI) preoperative findings have been found to be associated with a higher tumour recurrence rate in transplanted patients.
Machine-learning MRI models have the potential ability to extract information from unstructured medical imaging data and might be of predictive value for cancer recurrence but whether this approach is of value for HCC is uncertain and was the purpose of the present study.
Researchers retrospectively analysed data from a cohort of patients with HCC treated by liver transplant, surgical resection or thermal ablation and who had undergone pre-and post-treatment MRI scans. The US and German team trained a machine-learning MRI system to extract imaging features and developed three predictive models.
The first used imaging-derived data only, the second clinical and laboratory individual patient data and a final model, combined the imaging and clinical/laboratory data. The risk of HCC recurrence was predicted over a 6 year period after a patient’s first-line treatment. The predictive value of the different models were assessed based on the area under the receiver operating characteristic curve (AUC).
Machine-learning MRI model and prediction of HCC recurrence
The study included 120 patients with a mean age of 60 years (26.7% male) of whom, 36.7% experienced tumour recurrence during follow-up, with the mean time to recurrence being 26.8 months.
The highest AUC for each of the three models was achieved for the periods 4 and 6 years after treatment. After 6 years, the AUC for the clinical model was 0.69 (95% CI 0.54 – 0.84), 0.85 (95% CI 0.75 – 0.95) for the imaging model and 0.86 (95% CI 0.76 – 0.96) for the combined model.
Over the 6-year period the mean AUC for the imaging model was 0.76, 0.68 for the clinical model and this difference was statistically significant (p = 0.03) although the AUC for the combined model was the same as the imaging model (0.76).
Turning to the individual patient data, the clinical model correctly predicted 25% of recurrences, whereas the imaging model and combined models, both corrected predicted 87.5% of recurrences.
The authors concluded that a machine-learning MRI model could successful predict recurrence of early-stage HCC and that this model was superior to the use of clinical data alone and called for prospective cohort studies to externally validate these algorithms prior to clinical use.
Citation
Iske S et al. Machine-Learning Models for Prediction of Posttreatment Recurrence in Early-Stage Hepatocellular Carcinoma Using Pretreatment Clinical and MRI Features: A Proof-of-Concept Study AJR Am J Roentgenol 2022
27th July 2022
Combining an additional magnetic resonance imaging (MRI) and computed tomography (CT) scan in patients presenting with an acute ischaemic stroke, does not lead to better patient outcomes at both discharge and 12 months later, according to the findings from a retrospective study by US researchers.
Data from 2017 show that there were 1.12 million incident strokes in the European Union, 9.53 million stroke survivors, 0.46 million deaths, and 7.06 million disability-adjusted life years lost because of stroke. Patients who present with an acute ischaemic stroke (AIS) are normally initially evaluated with a CT scan to exclude haemorrhage.
Moreover, according the the American Heart Association/American Stroke Association guidelines, in patients who are suspected of having ischaemic stroke, if CT or MRI does not demonstrate symptomatic cerebral infarct, follow-up CT or MRI of the brain is reasonable to confirm diagnosis. In support of this recommendation, there are already some data to indicate that the use of MRI scanning in patients with an AIS is associated with substantial decrease in the rates of inpatient mortality and complications.
However, whether combining a CT scan with an additional MRI improves outcomes for patients is less clear. To date, only a single study has examined the effect of a CT scan and an additional MRI scan on patient outcomes, concluding that the long-term (one-year) patient outcomes may not be influenced by either imaging strategy.
In trying to better understand the value of a strategy that combined a CT scan with an additional MRI scan, in the present study, the researchers undertook a retrospective, propensity score matched study of the clinical outcomes at both discharge and one year later, for patients hospitalised with an AIS.
For the outcomes of interest, the researchers used either death or dependence at discharge, based on the Modified Rankin scale (mRS) which assesses disability in patients who have suffered a stroke. The scale ranges from 0 (no disability) through 5 (requiring constant care) to 6 (death) and the researchers set a non-inferiority margin of -7.5%, for the percentage of patients discharged with a mRS score of 3 to 6. For death, the researchers set a relative risk, RR of 0.725 as the margin for non-inferiority.
Additional MRI and clinical outcomes
A total of 246 patients (123 with and without an MRI scan) and a median age of 68 years (53% male) were included in the study. Among those who had an additional MRI scan, this was ordered by the attending vascular neurologists in 42.3% of cases, 33.3% by emergency physicians and 24.4% by nurse practitioners. In 111 cases of the 123 MRIs ordered, there was no specific indication other than either a stroke or neurological symptoms.
For the primary endpoint of a mRS score 3 – 6 at discharge, there was no significant difference between the two groups (relative risk, RR = 1.50, 95% CI 0.86 – 1.05, p = 0.44), with an absolute difference of 5.7%, thus meeting the -7.5% difference criteria for inferiority.
Stoke or death at one year after discharge occurred in more patients receiving the additional MRI compared to those who only had a CT scan (19.5% vs 12.5%), giving a RR of 1.14 (95% CI 0.86 – 1.50) thus again meeting the RR of 0.725 criteria for non-inferiority.
The authors concluded that the value of an additional MRI to a CT scan in patients with AIS should not be presumed and called for future studies to identify which patients hospitalised with an AIS may benefit from an MRI scan.
Citation
Frade HC et al. Comparison of Outcomes of Ischemic Stroke Initially Imaged With Cranial Computed Tomography Alone vs Computed Tomography Plus Magnetic Resonance Imaging JAMA Netw Open 2022
27th May 2022
Changes in brain connectivity during treatment for depression with transcranial magnetic stimulation (TMS) and which improve symptom scores can be seen during an MRI scan. This was the key finding of a study by a team of researchers from Canada and the US.
Depression affects an estimated 3.8% of the world’s population and a 2022 meta-analysis found the point prevalence of major depression to be 8%.
Repetitive transcranial magnetic stimulation (TMS) is a non-invasive technique which uses magnetic pulses to influence the excitability and connection strength of the cortical neurons and has been used as a treatment modality for major depression. It involves placing an electromagnetic coil on the scalp and delivery of a brief pulsatile magnetic field that depolarises cortical neurons.
Treatment with TMS has been shown to be effective for reducing suicidal ideation and in alleviating depression. The treatment is normally applied to the left or right dorsolateral prefrontal cortex (DLPFC) although use on either side appears to be equally effective.
The mode of action for TMS remains uncertain although the effects of TMS on brain activity that can now be studied by combining it with neuroimaging methods such as functional magnetic resonance imaging.
In a 2020 study combining TMS with MRI imaging, researchers observed how the magnetic stimulation induced lasting connectivity and excitability changes such that after treatment, the DLPFC appeared better able to engage in top-down control of the amygdala.
However, the particular changes in brain connectivity affected by TMS among those with major depression are unknown.
For the present study, the team wanted to visualise these changes with MRI but also determine whether such changes led to a clinical response in patients with major depression. They recruited adults with major, treatment-resistant depression and performed an open-label trial of TMS. The team initially acquired MRI scans without TMS and compared these to scans when TMS was delivered.
The treatment was applied to the right DLPFC once daily for a period of 4 weeks. The TMS-induced changes were assessed by pairwise comparison between the MRI scan with and without TMS. Depression symptoms were assessed using the Montgomery-Asberg Depression rating scale (MADRS) which was measured at baseline and at the end of the study.
Transcranial magnetic stimulation and depression
A total of 38 patients with a mean age of 41.8 years (68% female) were included in the study.
When comparing the two scans, the researchers observed 43 edges that were changed after use of TMS with a preponderance of inter-hemispheric functional connectivity. As the changes were absent from the baseline MRI scan, these were indicative of the response to TMS and hence an index of short-term macro-scale neuroplasticity.
The observed TMS-induced changes were short-lived and the authors suggested that repeated stimulation might be necessary to induce long-lasting connectivity effects.
More importantly however, the observed were associated with an improvement in depression symptom scores, with a drop in MADRS of 10.87.
The authors concluded that the observed TMS-induced effect on connectivity may index macro-level neuroplasticity changes and which might be indicative of an individual’s response to TMS treatment.
They called for further studies to assess the generalisability of these findings and their relevance to connectivity changes after repeated TMS therapy.
Citation
Ge R et al. Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial Am J Psychiatry 2022
11th February 2022
Elevated generalised and visceral body fat levels seen on a magnetic resonance imaging scan have been found to be associated with reduced cognitive scores even after adjustment for cardiovascular risk factors. This was according to a study by researchers from the Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Canada.
Increased levels of body fat and in particular central adiposity, measured by the waist-to-hip ratio, has been found to have a highly significant association with myocardial infarction risk. The use of magnetic resonance imaging (MRI) enables the detection of visceral fat volume and accumulated evidence shows that visceral adipose tissue is an independent risk marker of cardiovascular and metabolic morbidity and mortality. However, whether elevated levels of both generalised and visceral fat are linked with an impairment of cognitive functioning remain unclear. One prospective study of older adults concluded that abdominal fat in late life appears to confer an increased risk for dementia and cognitive impairment and where body fat levels have been assessed through electrical impedance, visceral fat accumulation was also associated with mild cognitive impairment. In contrast, however, a study in 1047 individuals aged 60 years and older concluded that abdominal obesity might be a protective factor for cognitive function.
With some uncertainty over the relationship between generalised and visceral fat and cognitive function, the Canadian team set out to examine this relationship based on MRI scan results. They turned to data from the Canadian Alliance of Healthy Hearts and Healthy Minds and the Prospective Urban Rural Epidemiological–Mind (PURE-MIND) studies. These studies recruited adults between the ages of 30 and 75 years of age and who had their body fat levels measured by bioelectrical impedance and MRI of the abdomen to measure visceral adipose tissue levels. In addition, all participants underwent MRI of the brain to measure vascular brain injury and cardiovascular risk factors were assessed using lifestyle questionnaires and physical measures. Cognitive assessment was measured using the Digital Symbol Substitution Test (DSST) and the Montreal Cognitive Assessment (MoCA). The DSST scores range from 0 to 133 with lower scores indicative of worse performance. In contrast, the MoCA score ranges from 0 to 30, with higher scores denoting normal cognitive function.
Generalised and visceral body fat levels and cognitive impairment
A total of 9189 adults with a mean age of 57.8 years (56.4% women) were included in the analysis. The women had a higher percentage of body fat compared to men (35.6% vs 25.1%) although men had a higher mean visceral adipose tissue volume (83.6 vs 64.1 ml). The mean DSST score was 72.6 and the MoCA score was 27 and both were slightly higher in women compared to men.
Overall, both a higher total percentage of body fat and visceral adipose score were associated with the lowest DSST score although this was not the case for visceral adipose scores and the MoCA. In regression models fully adjusted for age, sex, educational level and cardiovascular risk factors, the total percentage of body fat remained independently associated with reduced cognitive scores. The authors calculated that for each standard deviation increase in adiposity (9.2% for generalised fat and 36ml of visceral fat), there was a reduction of 0.8 in the DSST score, which was equivalent to 1 year of cognitive ageing. For example, comparing individuals in the highest versus the lowest percentage of body fat, was equivalent to 2.8 years of cognitive ageing. A similar amount of cognitive ageing was also seen between the highest and lowest levels of visceral adipose tissue. However, there were no significant associations between either total body or visceral fat with MoCA scores.
The authors concluded that based on these finding, excess adiposity was a risk factor for reduced cognitive scores and called for strategies to reduce or prevent adiposity as a means of preserving cognitive function in adults.
Citation
Anand SS et al. Evaluation of Adiposity and Cognitive Function in Adults JAMA Netw Open 2022
10th December 2021
A number of atrophic changes detected with magnetic resonance imaging (MRI) in patients with chronic traumatic encephalopathy (CTE) could be an important marker of the disease if observed in living patients. This was the tentative conclusion of a study by a team from the Framingham Heart Study, Boston University School of Medicine, Boston, US.
CTE is defined as a progressive neurodegenerative disorder linked to repetitive traumatic brain injury from head impacts and is a common finding in deceased, retired American football players. The pathognomonic lesion of CTE is an abnormal accumulation of hyper-phosphorylated tau protein (p-tau) within neurons and a definitive diagnosis can only be made by post-mortem examination of brain tissue. Furthermore, CTE has been categorised into four pathological stages of CTE, stages I (mild) to IV(severe), based on the density and regional deposition of p-tau.
Although imaging studies in living patients at a higher risk of CTE such as former American football players have revealed some changes, these studies could not definitively characterise the specific in vivo structural MRI patterns of CTE.
For the present study, the US researchers turned to MRI scans of patients with autopsy confirmed CTE together with a brain samples obtained from patients with normal cognition to compare atrophic changes. The researchers were interested in testing the associations between p-tau severity in those with CTE with atrophy changes seen on MRI. The neuropathological evaluations were undertaken by three neurologists, blinded to clinical data from the participants and who rated regional atrophy changes on a scale of 0 (none) to 4 (severe) in 14 different regions. In addition, the presence of cavum septum pellucidum (CPS), which is a common neuropathological feature of chronic traumatic encephalopathy, was recorded on a binary (absent/present) scale. For their analysis, the researchers used linear regression models to compare the brains of those with CTE and normal cognition donors. For those with CTE, the regression models examined the association between p-tau severity and atrophy changes seen on MRI.
Findings
A total of 55 donors with CTE and 31 men (11 who were deceased) with normal cognition were included in the analysis. The mean age at the time of the scan was 71 years for donors with CYE and 76 for those with normal cognition. In the majority of cases (65%), the MRI scan had been requested in CTE donors because of dementia or neurodegenerative disease. Among those with normal cognition, requests for the scans were for a wider range of conditions including cardiovascular causes (22.6%) and memory complaints (16.1%).
Compared to those with normal cognition, CTE donors had greater mean differences in atrophic changes in a number of areas. For example, orbital-frontal atrophy (mean difference, MD = 1.29, p = 0.009), dorsolateral frontal (MD = 1.31, p = 0.013), superior frontal (MD = 1.05, p = 0.046) and anterior temporal (MD = 1.57, p = 0.009). There were no differences for posterior atrophy or microvascular disease. In addition, among donors with CTE, there was a 6-fold increased odds of CSP (Odds ratio, OR = 6.7, p < 0.05) and a greater degree of tau severity across the different regions of the brain which was associated with a greater total brain atrophy on the MRI scan.
The authors concluded that in men with autopsy-confirmed CTE, there was more severe atrophy changes and more severe p-tau pathology. They suggested that if validated with prospective studies, their findings could support the use of structural MRI as a valuable tool to support a diagnosis of CTE during life.
Citation
Alosco ML et al. Structural MRI profiles and tau correlates of atrophy in autopsy-confirmed CTE. Alzheimers Res 2021 Ther
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