Superb microvascular imaging for detecting carpal tunnel syndrome compared with power Doppler ultrasonography

Abstract Background: Sonography enhances diagnostic accuracy by the detection of the epineural or intraneuronal blood flow.[1–4] Power Doppler ultrasonography (PDUS) in carpal tunnel syndrome (CTS) has been previously studied and shown to be valid and reliable for grading the intraneural flow.[3,4] However, superb microvascular imaging (SMI) represents a new era in diagnostic sonography, and this new technology enables accurate visualization of vascular structures with intensive clutter suppression to provide flow signals for large to small vessels, and it presents these data at high frame rates.[5–7] Studies suggested that SMI is more sensitive in demonstrating blood flow in the diagnosis of CTS compared with PDUS.[7] In order to gain clarity, a meta-analysis to systematically review and synthesize relevant data on the evaluating intraneural blood flow of the median nerve (MN) using SMI and PDUS was undertaken. Methods: We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to the December 31, 2020, without language restrictions. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata 14.0 software will be used for data analysis. Results: This systematic review will investigate whether superb microvascular imaging is more sensitive to display the blood flow in the MN with CTS than PDUS. Conclusion: Its findings will provide strong evidence for the feasibility of superb microvascular imaging on the detection of the neovascularization of the MN with CTS. Systematic review registration: INPLASY202110018.


Introduction
Carpal tunnel syndrome (CTS) is the most commonly diagnosed compression neuropathy of the upper extremity, that is, the median nerve (MN) is pressured at CTS which causes symptoms related to nerve damage. [8,9] The diagnosis of CTS is based on a combination of characteristic symptoms and electrophysiologic testing. [10] electrophysiologic testing can provide objective diagnosis basis, which has very high specificity. However, it will cause 10% to 25% false negative, especially for the early CTS. [10,11] Power Doppler ultrasonography (PDUS) in CTS has been previously studied and shown to be valid and reliable for grading the intraneural flow, [3,4] but Doppler technologies have low sensitivity for the blood flow so that it cannot show small, low speed blood flow signals. [12] Superb microvascular imaging (SMI) adopts a multidimensional filter to eliminate only the clutter and to preserve low-velocity flow signals, whereas conventional Doppler systems use a single-dimension filter and, accordingly, can exhibit a loss of low-velocity flow signals that overlap with clutter, which provides valuable information for clinical treatment. Studies suggested that superb microvascular imaging is valuable for the diagnosis of the CTS. [7,13,14] Therefore, the present meta-analysis aimed at accessing whether superb microvascular imaging is more sensitive to display the blood flow in the median with CTS than PDUS.

Materials and methods
This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines and the protocol was registered in the INPLASY (INPLASY202110018). 2.1.4. Type of outcomes. The primary outcomes include a semiquantitative scoring system, through which CTS was graded by means of both SMI and PDUS.

Search methods
PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases will be searched from their inceptions to the December 31, 2020, without language restrictions. The search strategy for PubMed is shown in Table 1. Other online databases will be used in the same strategy.

Data extraction and quality assessment
Two authors will independently select the trials according to the inclusion criteria, and import into Endnote X9. Then remove duplicated or ineligible studies. Screen the titles, abstracts, and full texts of all literature to identify eligible studies. All essential data will be extracted using previously created data collection sheet by 2 independent authors. Discrepancies in data collection between 2 authors will be settled down through discussion with the help of another author. The following data will be extracted from each included research: year of article, first author's surname, sample size, number of microvascular flow grades within the MN, number of every grade. The quality of selected studies will be independently evaluated according to a tool for the quality assessment of methodological index for non-randomized studies (MINORS). The MINORS criteria included 12 assessment items. Each of these items is scored as "yes" (2), "no" (0), or "unclear" (1). MINORS score ranged from 0 to 24; and score ≥17 indicate a good quality. Any disagreements between 2 investigators will be solved through discussion or consultation by a 3rd investigator.

Statistical analysis
The STATA version 15.1 software (Stata Corporation, College Station, TX) will be used for meta-analysis. We calculated the pooled summary odds ratio and its 95% confidence interval. The Cochran's Q-statistic and I 2 test will be used to evaluate potential heterogeneity between studies. [15] If the Q test shows a P < .05 or I 2 test exhibits >50%, indicating significant heterogeneity, and the random effect model will be employed or if heterogeneity is not significant, the fixed-effects model was used. If it is possible, we will perform meta-analysis to analyze the pooled outcome data when acceptable homogeneity has been identified. Otherwise, we will conduct subgroup analysis to investigate potential causes for substantial heterogeneity among eligible studies. Sensitivity analysis will be performed to evaluate the influence of a single study on the overall estimate. We will use Begger funnel plots and Egger linear regression test to investigate publication bias. [16]

Ethics and dissemination
We will not obtain ethic documents because this study will be conducted based on the data of published literature. We expect to publish this study on a peer-reviewed journal.

Discussion
Since the 1990s, the American Academy of Neurology has recommended ultrasound examination of the MN for the diagnosis of CTS. [17] The MN is provided by a rich anastomotic system of epineural and endoneural blood vessels, which extends vertically from epineuria to fascicular. The increase of the microvessels density because of enhanced proliferation of Table 1 Search strategy sample of PubMed. Schwann cells and vascular endothelial growth factor is responsible for regeneration of the entrapped MN. Doppler US showed the blood flow signals in the MN of the CTS increased. [18][19][20][21] When compared with power doppler, the sensitivity and finer detail of the microvessels can be visualized with SMI appears significantly better. The potential clinical value of this advanced technology and how it could significantly change clinical management were illustrated in several researches. [14,22] To gain clarity, in this study, we will perform a systematic review to summarize high-quality studies and to provide evidence on the evidence-based medical support for clinical practice.