The Combination of Stent and Antiplatelet Therapy May Be Responsible of Parenchymal Magnetic Susceptibility Artifacts after Endovascular Procedure
, Douraied Ben Salem 1,4, Jean-Christophe Gentric 1,2 and Julien Ognard 1,4,*Round 1
Reviewer 1 Report
This is an important manuscript showing the effect of stent therapy on magnetic susceptibility artifacts. Here are some suggestions to help improve the paper.
1) Although the focus of this manuscript was on the magnetic susceptibility, it would be helpful to see the results of the 3D time of flight scans (which scans are mentioned in the methods section) especially if those scans can add information to characterize the brain tissue damage caused by the microbleeds. How did the blood flow or blood vessels change near the MSA?
2) It would also be helpful to add a correlation of MSA versus clinical severity of disease. Was a clinical score assessed from each patient before and after therapy?
Author Response
Reviewer #1
This is an important manuscript showing the effect of stent therapy on magnetic susceptibility artifacts. Here are some suggestions to help improve the paper.
Thank you very much for your grateful comment.
1) Although the focus of this manuscript was on the magnetic susceptibility, it would be helpful to see the results of the 3D time of flight scans (which scans are mentioned in the methods section) especially if those scans can add information to characterize the brain tissue damage caused by the microbleeds. How did the blood flow or blood vessels change near the MSA?
Thank you for your remark. The blooming artifact produced by the MSA were not sufficient to affect the reading of any TOF. This may not place the TOF sequence to be helpfull, but it reinforces the hypothesis that these MSA are probably microhemorrhagic, or eventually linked to very very small paramagnetic material. Postprocessing of SW imaging involves multiplication of magnitude images with high-pass filtered phase images to enhance depiction of hemosiderin deposits. Phase information facilitates distinction of microbleeds from mimics such as calcification, microdissections, microaneurysms, microcalcifications, and arteriolar pseudocalcifications. The point you raised is of interest and we added this sentence to emphasize :
« All described MSAs were described in the phase imaging as having the same behavior as microbleeds, which excluded mimics such as microdissections, microaneurysms, microcalcifications, and arteriolar pseudocalcifications. In addition, the study of all available sequences described a restricted blooming artifact. »
2) It would also be helpful to add a correlation of MSA versus clinical severity of disease. Was a clinical score assessed from each patient before and after therapy?
We have clinicaly reviewed every cases. In our center, during the consultation (pre and post therapeutic) a modified Rankin Scale is systematically assess. There were mild changes in this score in the population, but everytime related to the procedure (complication) or related to an external event. No changes of the mRS could have been linked to the presence of MSA, and futhermore no changes in T2FLAIR were noticed surrounding these lesions.
This statement is resumed in the 3.3 : « According to the review of radiological and clinical data, none of the MSA were symptomatic. These MSA findings did not change any dual antiplatelet protocol. There were no abnormalities of signal on 3D T2 FLAIR weighted imaging around MSA, and study of DWI revealed no recent ischemic lesion in these areas. »
Nevertheless, the mRS scale may not reflect slight changes in the cognition of the patient, like more precise clinical scale (dedicated neuropsychologic tests, MMSE etc…). And, the cognitive repercussions of cerebral microbleeds are a matter of debate. The two prevailing hypotheses are that they either affect brain functioning through strategic disruptions of connections between brain regions, or that the underlying brain pathology—of which microbleeds are reflective—causes (sub)clinical deficits. This is why, we corrected the last sentence of the manuscript :
« Long-term follow-up of these patients would also make it possible to evaluate the risk of late hemorrhagic complication or clinical deficit, to see if the findings described in this study may lead to events or if they are purely incidentals. »
Reviewer 2 Report
The manuscript presents a comparison between the occurrence of magnetic susceptibility artefacts in patients who underwent stent placement or had coiling alone as a treatment of intracranial aneurysm. Although, as the same authors admit, the study could take advantage of the analysis of further important factors (e.g. device type, arterial blood pressure, different antiplatelet management, etc.), nonetheless these preliminary results look interesting, properly obtained and well reported.
There are a few typo's or unclear statements to correct:
- p. 6, l. 208, "[16";
- p. 6, l. 224, "patients on platelet antiplatelet therapy";
- p. 6, l. 230-232, "the fact remains that an almost perfect agreement between the observers was found reinforces the presumption of reality of the phenomenon";
- p. 7, l. 250, "This may also confirms";
- p. 7, l. 255, parenthesis never closed.
Moreover, I have a couple of questions for the authors about some details not clear from the text:
- The fact that the number of female patients was exactly the same in both the S- and C-group is a coincidence or was it deliberate? In the second case, why?
- Since the MR images taken to detect MSAs are T2-weighed, could the MSAs be due to iron (ferromagnetic material)?
- Would the use of a MRI contrast agent help to identify early the presence of MSAs, thus letting intervene promptly to adjust the therapy?
Author Response
Reviewer #2
The manuscript presents a comparison between the occurrence of magnetic susceptibility artefacts in patients who underwent stent placement or had coiling alone as a treatment of intracranial aneurysm. Although, as the same authors admit, the study could take advantage of the analysis of further important factors (e.g. device type, arterial blood pressure, different antiplatelet management, etc.), nonetheless these preliminary results look interesting, properly obtained and well reported.
Thank you very much for your grateful comment.
There are a few typo's or unclear statements to correct:
- 6, l. 208, "[16";
Corrected to « [16] »
- 6, l. 224, "patients on platelet antiplatelet therapy";
« patients on platelet antiplatelet therapy » corrected to « patients under antiplatelet therapy »
- 6, l. 230-232, "the fact remains that an almost perfect agreement between the observers was found reinforces the presumption of reality of the phenomenon";
This was corrected to :
« the fact remains that an almost perfect agreement between observers has been found. This reinforces the presumption of reality of the phenomenon »
- 7, l. 250, "This may also confirms";
Grammar was corrected :
« This may also confirm that the occurrence of MSA is multifactorial. »
- 7, l. 255, parenthesis never closed.
« (in 91.7% of cases (44 out of 48) in the study of Hahnmann [21] and in 100% of the cases in the study of Heller [27]) »
Moreover, I have a couple of questions for the authors about some details not clear from the text:
The fact that the number of female patients was exactly the same in both the S- and C-group is a coincidence or was it deliberate? In the second case, why?
It was deliberate. From ou database we managed to find control –coiled- patients with the same proportion of men/women and ages (Mean C-Group 55yo and Mean S group 53yo). This allowed us to match the population with these cofactors, even though, as you also pointed out, we did not push the minimization on other covariates such as cardiovascular risk factors.
( 2.1 Section patients : « A one for one control group was also retrospectively constituted minimizing the age and sex differences of all patients between both groups. The same data were recorded keeping the same exclusion criterion for these patients which had to be treated solely by coils (C-group, n=46). »)
Since the MR images taken to detect MSAs are T2-weighed, could the MSAs be due to iron (ferromagnetic material)?
Yes, the signal loss results from intravoxel dephasing because of local perturbation of the main magnetic field, in turn caused by high concentrations of iron. Thank you for this remark. This last point was raised in the discussion section. However, your comment made us think that the sentence was not explicit enough, so we have reworded it.
« It is also possible that these MSA correspond to emboli of used equipment [30]. This last hypothesis support the results that MSA tended to appear the most in the first 3 months but continued to appear during the follow-up. » Was changed to : « It is also possible that these MSA correspond to emboli of used equipment, as ferromagnetic material or polyvinylpyrrolidone (PVP), a substance that is commonly used in the coatings of interventional devices »
- Would the use of a MRI contrast agent help to identify early the presence of MSAs, thus letting intervene promptly to adjust the therapy?
We believe that an enhanced MRI could eventually help predict the evolution of the brain parenchyma. If it is an ischemic spot, there could be a barrier disruption phenomenon on the MRI that could indicate tissue fragility that would be secondarily sensitive to antiplatelet agents (and therefore would result in a second stage of hemorrhagic microrearrangements), However, in routine, it is not common to have an MRI immediately after the endovascular securing procedure, let alone an enhanced MRI, although this protocol could advance the pathophysiological understanding of the development of MSA. But already with diffusion sequences in non-enhanced MRI, we could have arguments in favor of ischemic or non-ischemic etiology if MRI was systematic and performed early after the procedure.
Therefore, we introduced this sentence in the end of the discussion section, as a moderation of this point: "In order to distinguish the different etiologies mentioned above, it may be appropriate in a future study to systematize an MRI after endovascular procedures.
