Microhemorrhages in Traumatic Brain Injury May be Missed if Imaged too Late

This week's featured research article continues the focus on cerebral microbleeds (CMBs). Since they are a relatively new medical finding, much information is still unknown about their characteristics over time. What is known is that susceptibility weighted imaging (SWI) is a more sensitive MRI sequence than the traditional gradient recalled echo (GRE) T2* sequence at detecting and characterizing bleeds. While the former is used often in the research setting, it's usage in the clinical setting has not gained much traction. Further, the raw magnitude and phase data from the SWI sequence can be post-processed to create a Quantitative Susceptibility Map (QSM, or Susceptibility Weighted Imaging Map (SWIM)). A QSM represents underlying susceptibility of the brain tissue. It is more accurate than the phase information, because it is an intrinsic tissue property which is independent of the data acquisition parameters, and devoid of phase artifacts. With a QSM or SWIM image, one can detect and quantify CMBs along with their location and volume. Magnetic susceptibility from blood products in lesions yields bright signal in QSM. The image can also discriminate between paramagnetic regions like iron-laden and diamagnetic regions like calcium, which are easily confused which true bleeds due to their similar hypo-intense appearance in SWI.

The following study out of Radiology longitudinally evaluates cerebral microhemorrhages in a cohort of US military service members who have chronic TBI using SWI. It has been estimated that 10-20% of military personnel who have been deployed in Iraq and Afghanistan have experienced TBI, with most cases (80%) being in the mild state. Even mild TBI cases have shown subtle venous damage and microbleeding. 

Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury. Wei Liu, et al. Radiology , 2015.

Within the study, 603 service members were recruited who have had TBI in severe (1.5%), moderate (5.8%), and mild (92.7%) cases.

MRI data were collected on a 3T GE scanner with a protocol which included GRE, and flow-compensated multiecho  GRE imaging. Typically, SWI can be run from a Siemens scanner, however, in this case the data were constructed using SPIN Software (MR Innovations, Detroit, MI).  The QSM images were processed using morphology-enables dipole inversion, or MEDI approach.  Some of the patients also underwent follow-up scans at 6-month, 12-month, and 36-month periods after the injury date.  

Two radiologists reviewed the GRE, SWI, and QSM data for microbleeds and found 43 of the patients (7.1%) showed at least one CMB. The SWI data showed higher sensitivity at detecting bleeds compared to the GRE data (585 hemorrhages detected vs. 362) and generally appeared on SWI with more conspicuousness. This finding confirms work by Cheng et. al (Stroke 2013).

Figure 1: A, GRE, B, SWI, and, C, QSM images in a patient with TBI. The arrows indicate a CMH that is visible on SWI, GRE, and QSM images. The arrowheads indicate another CMH that is visible on SWI and QSM images, but not the GRE image. ppb = parts per billion.

The majority of the bleeds could be found in the frontal subcortical region (30%), parietal subcortical region (15%), and the temporal subcortical region (14%). 

A, SWI and, B, QSM images show the evolution of microhemorrhages (arrows) in a patient who underwent follow-up imaging. Each column from left-right represents 6-months after injury, 12-months after injury, and 36-months after injury,

Plot of the mean magnetic susceptibility of microhemorrhages in individual patients who underwent follow-up imaging.  The results show that mean susceptibility of  CMBs decreases over time. 

The longitudinal assessment also showed that bleed counts, volume, and mean susceptibility decreased over time, which for the first time shows the evolution of CMBs in the chronic stage. Volumes decreased at a rate of -0.85 mm³ ± 1.59 per day (P = .039) and -0.10 parts per billion per day ± 0.14 for mean magnetic susceptibility (P =.016).

The prevailing thought is that the brain is incapable of removing hemosiderin iron once it is deposited in a lesion, however, this new research shows lesion changes which implies that hemosiderin blood products undergo continued subtle changes over time. 

The authors concluded that:

For the identification of the presence or absence of cerebral microbleeds, SWI should be the method of choice in a clinical setting. It is critical to image a TBI patient as close to the injury date as possible, otherwise subtle damage may me missed.

The diagnostic sensitivity of SWI married with the quantitative information of QSM shows great power in tracking the progress of TBI in the chronic state.  

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MR Innovations is on the cutting edge of quantitative MRI post-processing software and analysis including SWI data construction, and Quantitative Susceptibility Mapping, please visit www.mrinnovations.com.

References:

1.   Liu W, Soderlund K, Senseney JS, et al. Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury. Radiology 2015:150160.

Susceptibility Weighted Imaging in Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) can be classified as a loss of consciousness and/or confusion and disorientation is shorter than 30 minutes.  While MRI and CAT scans are often normal, the individual has cognitive problems such as headache, memory problems, attention deficits,  mood swings and frustration.  While the condition may be called “mild,” the effects can be devastating. This week’s paper discusses findings in mTBI subjects with a sensitive MRI sequence called susceptibility weighted imaging (SWI) which can detect subtle findings such as venous damage, and cerebral microbleeds when other scanning modalities cannot.

Susceptibility weighted MRI in mild TBI, Huang et al. Neurology, 2015

SWI images depecting microbleeds (white arrows).

In Neurology Today, a review of SWI in mTBI appears by Richard Robinson. He interviewed Dr. Chi-Jen Chen from Taipei University and Mark Fisher from UCI. According to Huang et al, cerebral microbleeds (CMBs) are common in mTBI as seen by SWI. Although many mTBI patients recover well, there is a cohort who suffer from prolonged disability. There has been a lack of imaging biomarkers as prognostic factors for mTBI.  A separate editorial appears by Drs. Haehnel and Herweth about the role of SWI in detecting CMBs in mTBI. SWI is a method developed by Prof. E. Mark Haacke and is exquisitely sensitive to venous blood and blood products such as hemosiderin (which is the major constituent of CMBs).

Dr. Chen enrolled 111 patients and age matched controls who were negative for hemorrhage on CT and conventional MRI. They found 60 CMBs in 26 patients and only 15 CMBs in 12 healthy controls. In mTBI patients, 87% were in the cortex and sub-cortical white matter while only 20% of the CMBs in healthy controls were in the same region. The rest were in the deep gray matter and may have been associated with hypertension.

Dr. Chen suggests that CMBs may serve as a biomarker for mTBI. They found that there was a correlation with neuropsychological testing for memory and the number of CMBs.  

Dr. Fisher suggested that further work be done to see if there is an association of CMBs with loss of consciousness, fMRI results and age.

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MR Innovations is on the cutting edge of detection, location, and quantification of cerebral microbleeds. For more information on SWI and MRI post-processing and analysis, please visit www.mrinnovations.com.

References:

1.    Huang YL, Kuo YS, Tseng YC, Chen DY, Chiu WT, Chen CJ. Susceptibility-weighted MRI in mild traumatic brain injury. Neurology. 2015 Feb 10;84(6):580-5.

Cerebral Microbleeds Predict Poor Outcome After Intravenous Thrombolysis In Stroke Patients

SWI (a) and GRE (b) MRI images of a stroke case (2).

Continuing the topic of cerebral microbleeds from last week, a recent study by Yan and colleagues investigates the clinical relevance of the presence of CMBs in ischemic stroke patients when undergoing thrombolytic treatments:

Extensive cerebral microbleeds predict parenchymal haemorrhage and poor outcome after intravenous thrombolysis. Yan S, Jin X, et al. J Neurol Neurosurg Psychiatry. 201  

The purpose of this study was to evaluate the impact of CMB on clinical outcomes of ischemic stroke patients after thrombolytic treatments. Susceptibility weighted imaging was exclusively used to image patients before and after treatment with recombinant tissue plasminogen activator (rtPA). Two investigators blinded to 333 patients’ clinical data jointly reviewed the MRI findings for CMBs by frequency and location using detection criteria described by Greenberg et al. Analysis was done on the hemorrhagic transformation subtypes: hemorrhagic infarction (HI), and parenchymal hemorrhage (PH), extra-ischemic hemorrhage, and symptomatic intracranial hemorrhage (sICH). NIHSS scores independently predicted hemorrhagic transformation for HI, and PH. On SWI, 742 CMBs were detected in 133 patients.

The presence of ≥ 3 CMBs independently predicted parenchymal hemorrhage and poor clinical outcome after intravenous thrombolysis.

 
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MR Innovations is on the cutting edge of detection, location, and quantification of cerebral microbleeds. For more information on SWI and MRI post-processing and analysis, please visit www.mrinnovations.com.

References:

1. Yan S, Jin X, Zhang X, Zhang S, Liebeskind DS, Lou M. Extensive cerebral microbleeds predict parenchymal haemorrhage and poor outcome after intravenous thrombolysis. J Neurol Neurosurg Psychiatry. 2015 Jan 28. pii: jnnp-2014-309857. doi: 10.1136/jnnp-2014-309857. [Epub ahead of print]

2.  Kakar P, Charidimou A, Werring DJ. Cerebral microbleeds: a new dilemma in stroke medicine. JRSM Cardiovascular Disease. 2012;1(8):2048004012474754. doi:10.1177/2048004012474754.

Cerebral Microbleeds in Cerebral Amyloid Angiopathy

Susceptibility Weighted Image showing a CAA patient 

with numerous microbleeds. Collected at 1.5T. 

A hot topic currently is Cerebral Microbleeds (CMBs, aka cerebral microhemorrhages) which manifest in diseases and conditions such as vascular dementia, stroke, cerebral amyloid angiopathy (CAA), traumatic brain injury (TBI), and even normal aging. CMBs reflect small areas of hemorrhage. The small "microhemorrhages" consist pathologically of collections of hemosiderin-laden macrophages, often associated with diseased blood vessels. It has been suggested that cerebral microbleeds may be a risk factor for intracranial hemorrhage. A patient with a minimal number of bleeds may have a high risk of intracerebral hemorrhage if treated with anti-platelet and anti-coagulant drugs, thus it is critical to detect their presence before any treatment. T2*-weighted gradient-echo magnetic resonance (MR) imaging, specifically Susceptibility Weighted Imaging, is the method of choice for detecting cerebral microbleeds because of its sensitivity to the field inhomogeneity caused by hemosiderin deposits. 

Cerebral amyloid angiopathy: emerging concepts.Yamada M. Journal of Stroke. 2015;17(1):17-30. 

Cerebral amyloid angiopathy is a disease most prevalent amongst the elderly, affecting approximately half of them. It is associated with Alzheimer's disease with a prevalence of 80-90%. CAA is classified into several types depending on which amyloid protein is involved but this review primarily focuses on amyloid-beta protein. CAA can mostly be found in the leptomeningeal and cortical vessels of the cerebral lobes and cerebellum. The nature of the disease is vascular in which small and medium arteries accumulate amyloid deposits into the media and adventitia of the vessel wall. Derived from the brain, amyloid moves through periarterial interstitial fluid drainage pathways to blood vessels for clearance, but aggregates on the vascular basement membrane. CAA is significantly related to lobar cerebral macrohemorrhage, as well as cerebral microbleeds, and cortical superficial siderosis. CMBs are noted in 16.7% - 32 % of AD patients, which is much higher than the general population (5 - 6%)-when examined with T2* GRE MRI; it is also noted in 78% of AD patients or mild cognitive impairment on ultra-high field strength 7T MRI. Cerebral hypoperfusion (occlusive small vessel disease may cause white matter lesions in the occipital lobe, which can be seen with MRI. Dementia is also noted in 74% of several CAA. 

One can image CAA with multiple modalities, for example, inflammatory CAA is characterized by T2-hyperintense white matter lesions on MRI. For macrohemorrages cranial CT is an option, however, 

SWI (susceptibility weighted imaging) is one of the most sensitive MR imaging techniques for detecting CMBs. 

Cognitive impairment can be assessed with Doppler ultrasound and fMRI, consistent with the damage in the occipital lobe. Amyloid imaging with the PET ligand, PiB, reveals increased PiB binding which often shows greater occipital uptake of CAA-related intracerebral hemorrhage. Amyloid imaging, however, cannot discriminate between vascular from parenchymal deposition or Amyloid beta from other amyloid proteins. Biochemically, levels of the amyloid tau protein are higher in patients with probable CAA compared to controls, but lower than in AD. Amyloid beta -40 and -42 levels are significantly low in the CSF of CAA, which may suggest it being trapped in the cerebral vasculature. The Boston criteria are to be used when diagnosing CAA, but no disease-modifying therapies are available yet. The risk factors for CAA include old age, AD, blood-thinning and anti-thrombotic medications, hypertension, head trauma, CAA-related gene mutations, and apolipoprotein E gene in sporadic cases. Pathogenic mechanisms underlying the damage and rupture of CAA-affected vessels remain to be determined. 

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MR Innovations is on the cutting edge of detection, location, and quantification of cerebral microbleeds. For more information on SWI and MRI post-processing and analysis, please visit www.mrinnovations.com. 

References: 

1. Yamada M. Cerebral amyloid angiopathy: emerging concepts. J Stroke. 2015;17(1):17-30.