Detection of Cerebral Microbleeds With Venous Connection at 7-Tesla MRI
Abstract
Objective
Cerebral microbleeds (MBs) are a common finding in patients with cerebral small vessel disease (CSVD) and Alzheimer disease as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein.
Methods
7-Tesla (7T) MRI was conducted and MBs were counted on quantitative susceptibility mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein.
Results
A total of 51 people (mean age [SD] 70.5 [8.6] years, 37% female) participated in the study: 20 had CSVD (cerebral amyloid angiopathy [CAA] with strictly lobar MBs [n = 8], hypertensive arteriopathy [HA] with strictly deep MBs [n = 5], or mixed lobar and deep MBs [n = 7], 72.4 [6.1] years, 30% female) and 31 were healthy controls (69.4 [9.9] years, 42% female). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. Patients with CAA showed the highest ratio of venous to total MBs (19%) (HA = 9%, mixed = 18%, controls = 5%).
Conclusion
Our findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathologic studies are needed to confirm our observations.
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© 2021 American Academy of Neurology.
Publication History
Received: August 23, 2020
Accepted: January 28, 2021
Published online: March 2, 2021
Published in print: April 20, 2021
Disclosure
The authors report no disclosures/conflicts of interest. Go to Neurology.org/N for full disclosures.
Study Funding
Supported by the BMBF (EnergI-Consortium, TP01) and the German Research Foundation, CRC 779 (TP A07).
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We thank the authors for the attention dedicated to our study.1 This work reports the presence of microbleeds (MBs) with a spatial connection to veins, as observed on high-resolution Quantitative Susceptibility Mapping (QSM). As we openly discuss, we cannot exclude that this observed spatial relationship is not a casual one; only neuropathological correlation studies can provide certainty. Considering the predominantly arterial pattern of vascular amyloid-b accumulation in Cerebral Amyloid Angiopathy (CAA), alternative vessel pathologies—such as venous collagenosis2—are more likely to play a role.
In contrast to what Chen and Wang assert, MBs of venous origin were also found in deep/infratentorial regions in our cohort. Moreover, the authors point out that prevalence of MBs in healthy controls was considerably higher (81%), than reported in previous studies (~15%). This is true, but easily explained by the use of submillimeter-resolution, high-field(7T) MRI, at which higher sensitivity is expected.3 Since the Microbleed Anatomical Rating Scale (MARS),4 a score developed for lobar and deep MBs throughout a wide range of MBs burden, and a semiautomatic detection application5 were used, it is improbable that low burden of MBs affected our results. In conclusion, we think that all doubts expressed in the comment find a convincing explanation within the study itself.
Disclosure
The authors report no relevant disclosures. Contact [email protected] for full disclosures.
References
Rotta and colleagues performed a 7T MRI study and found that approximately 14% of microbleeds (MBs) were related to a venous source using a Quantitative Susceptibility Mapping (QSM) sequence,1 challenging the artery origin of MBs.2 We support the notion that a certain number of MBs are closely connected to veins, which can also be visualized with 3T MRI Susceptibility Weighted Imaging (SWI) or QSM techniques. Indeed, the microbleed connection with veins may be more prevalent in the cortex.1 However, one should be aware that MBs in the cortex are more difficult to differentiate from vessels than deep and infratentorial MBs, especially in individuals with mild MBs burden.3, 4 In the present study,1 the control group had a low microbleed burden, while 25 out of 31 healthy controls had at least one MBs presence (81%), which was higher than the prevalence reported from community studies (15%). It is possible that some vascular structures were misjudged as MBs in some patients.
Furthermore, we have found that MBs with a venous connection can also be seen in the basal ganglia and brainstem, which contrasts with this study’s finding.1 This difference may be due to inadequate power of detection for deep and infratentorial MBs. Insufficient power of detection may also explain the lower ratio of MBs with venous connection in controls, compared with patients with cerebral amyloid angiopathy (CAA).
Disclosure
The author reports no relevant disclosures. Contact [email protected] for full disclosures.
References