Diagnostics, Vol. 13, Pages 128: Clinical Applications of Quantitative Perfusion Imaging with a C-Arm Flat-Panel Detector—A Systematic Review

1. IntroductionInterventional radiology suites have traditionally used two-dimensional (2D) techniques such as digital subtraction angiography (DSA) for guiding operations and intervening on three-dimensional (3D) structures [1]. DSA is a fluoroscopic technique that enables the visualization of small vessels with small amounts of contrast through the means of image subtraction [2]. Advances in technology allowed the development of rotational DSA in which 3D volumes can be acquired in a single gantry rotation using cone-beam backprojection algorithms [3,4,5].Cone-beam computed tomography (CBCT) technology was incorporated in the late 1990s into experimental C-arm computed tomography (CT) systems using image intensifier systems based on a convolution-backprojection formula [1,6]. These image intensifier systems were later replaced with digital flat-panel detectors, which improved spatial and contrast resolution [7]. Nowadays, flat-panel detector C-arm systems are widely used in hybrid operating rooms and interventional radiology suites for treatment planning, intraoperative guidance, and intra-arterial therapy.Most pathologies encountered in the interventional suite and their targeted therapies have a direct effect on the dynamics of blood flow, raising the demand for a standardized and quantitative evaluation of tissue perfusion. In the diagnosis and treatment of vascular diseases, 2D DSA is the most often used imaging method [8,9,10]. Studies have demonstrated the feasibility of extracting quantitative perfusion data from 2D DSA through the means of parametric color coding [11,12,13,14,15,16,17] and time–density curve (TDC) analysis [18,19,20]. Furthermore, in patients with cerebral ischemia and hepatic malignancies, studies have investigated 3D volumetric imaging with flat-panel detector C-arm systems for quantifying perfusion using techniques such as multiphase CBCT perfusion [21] and dual-phase CBCT perfusion [22].

Quantitative perfusion imaging with C-arm systems is applied across a varied spectrum of diseases, from the detection of perfusion deficits in acute ischemic stroke to the treatment of liver tumors and peripheral arterial disease (PAD). The aim of this systematic review is to provide an overview of flat-panel detector C-arm techniques for quantifying perfusion, their clinical applications, and their validation against reference techniques.

4. Discussion

This systematic review provides an overview of the currently available C-arm flat-panel detector imaging techniques for quantifying perfusion in extracranial and extracardiac vascular pathologies. Of the nine included studies in this review, five investigated 2D perfusion angiography in the lower limbs of patients with PAD, and the remaining four investigated dual-phase CBCT perfusion in the liver in patients with HCCs. Weak-to-moderate correlations were reported between the C-arm techniques and reference techniques. In addition, most of the studies included small cohorts and demonstrated a relatively high risk of bias in the conduct and interpretation of the index and reference tests.

Two-dimensional perfusion angiography provided an objective approach to the real-time quantification of the hemodynamic status of patients with PAD through means of parametric color coding and TDC analysis. The clinical results of revascularization therapies are highly unpredictable, as evident by high failure rates and repeat interventions [45,46,47]. Currently, DSA serves as the gold standard for the evaluation of treatment success in endovascular therapy, and is conducted through a subjective visual evaluation of the run-off of the affected vasculature [48,49]. However, the prediction of the clinical outcome after endovascular therapy remains challenging, with no clear objective endpoints [50]. Studies have investigated non-invasive measurements for the prediction of the clinical outcome; however, the techniques were limited by their unavailability intraoperatively and the lack of strong correlations with wound healing [50,51]. Direct correlations were reported between 2D perfusion angiography parameters and pressure indices and transcutaneous oxygen pressure. Furthermore, this technique has demonstrated excellent reliability when used with a standardized injection protocol [40] and has the potential to predict the clinical outcome [52]. However, there are some limitations, including the following: dependency on the acquisition protocol [40], sensitivity to foot movements [18,19,20,40], and sensitivity to inflammatory processes and arterial spasms [40]. In addition, owing to the heterogeneity in acquisition protocols and lack of clinical follow-up in the literature, no uniform endpoints for therapy have yet been determined.The studies that applied 3D perfusion quantification techniques were in patients who underwent the hepatic arterial embolization of a liver tumor. The aim of these treatments is to maximize tumor devascularization, while causing minimal damage to liver parenchyma [53]. The primary endpoint of these therapies is overall survival [54,55]. No objective technique for the early prediction of the tumor response currently exists. Assessment is conducted postoperatively after one to three interventions via length measurements such as RECIST or mRECIST [56,57]. Therefore, enabling the early detection of the tumor response is valuable for assessment, follow-up, and treatment planning.Interventional oncology under C-arm guidance is increasingly becoming a standard treatment in patients with liver tumors [58,59,60]. The advent of dynamic functional imaging with dual-phase CBCT perfusion has made intraoperative functional imaging of the liver possible, leading to new opportunities for the early assessment of the tumor response. Studies have demonstrated the feasibility of using dual-phase CBCT perfusion imaging for the calculation of the PBV of liver and hepatic tumors and validated it against MDCTP [31,32,33,34]. Zhuang et al. [31] and Peynircioğlu et al. [32] included small cohorts and reported good correlations, whereas Syha et al. [34] and Rathmann et al. [33] reported weak to moderate correlations. The discrepancy in the correlations suggests that dual-phase CBCT perfusion and MDCTP measurements could indicate independent changes [33]. Despite this discrepancy, dual-phase CBCT perfusion has been demonstrated to have a similar capability to MDCTP in the assessment of PBV and tumor vascularity [31,32,33,34]. In addition, the assessment of PBV could potentially aid in predicting tumor response [34,41,61]. The combination of anatomical and functional imaging highlights the potential of using dual-phase CBCT perfusion for treatment optimization and the prediction of the treatment response. However, two dual-phase CBCT acquisitions could potentially expose these patients to a high radiation dose. In addition, determining the value of this technique is difficult due to the long-term nature of treatment, which usually necessitates that patients undergo several sessions or different therapies over a long period of time.

This study has some limitations. First, the lack of consensus regarding the terminology for C-arm systems and related perfusion techniques made it difficult to devise a search strategy inclusive of all related articles. To mitigate any possible loss of articles, the search included cross-checking the references of the relevant literature and was expanded to include as many synonyms and terms as possible. Second, none of the studies included in this review assessed the relationship between the perfusion parameters and primary clinical outcomes. Third, the studies investigating 2D perfusion angiography incorporated small cohorts and demonstrated a large heterogeneity in the reference technique, the calculated perfusion parameters investigated, and the acquisition protocols. Fourth, the value of the studies in this review that investigated dual-phase CBCT perfusion could not be determined due to a lack of long-term follow-up. Last, the heterogeneity between the studies made it impossible to draw conclusions and pool the data.

For future studies investigating these techniques, we advise using the following naming scheme to avoid confusion and loss of information. The term flat-panel detector C-arm CT is used to describe any modern C-arm CT machine in angiography suites and hybrid operating rooms, considering all angiography suites now are equipped with C-arm systems incorporating flat-panel detector technology. The term 2D perfusion angiography is used to describe the 2D DSA perfusion imaging technique that relies on TDC analysis for the extraction of quantitative perfusion data from conventional 2D DSA images. The term dual-phase CBCT perfusion is used to describe a 3D technique for quantitative perfusion imaging with a flat-panel detector C-arm through acquiring two rotational volumes. For studies investigating 2D perfusion angiography, we recommend using a standardized acquisition protocol [40], including larger cohorts, and investigating the relationship with primary clinical outcomes. For studies investigating dual-phase CBCT perfusion, we recommend including larger, homogenous cohorts with long-term follow up.

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