**1. Introduction**

Nowadays, abdominal tissue as the main source for breast reconstruction is preferably harvested either as a complete muscle-preserving deep inferior epigastric perforator (DIEP) flap or as a muscle-sparing transverse rectus abdominis musculocutaneous (ms-TRAM) flap [1,2]. The ability to reconstruct the female breast in a like-with-like fashion with low donor site morbidity has led to its widespread use [3]. Some of the latest tissue engineering and regenerative medicine methods aiming to overcome donor site sequelae are promising but not yet clinically feasible [4,5]. Although both DIEP and ms-TRAM flaps have overall low complication rates, partial flap necrosis and total flap loss due to vascular compromise remain imminent postoperative risks [6]. Sufficient vascular perfusion remains a key aspect for the overall outcome and flap survival. In the last few years, numerous clinical studies assessed the intra- and postoperative perfusion of free flaps using different technologies [7–14]. However, several studies aiming to understand the hemodynamics of free flaps showed methodological flaws such as a heterogeneous study population, small sample sizes of the included flap types in terms of tissue composition,

**Citation:** Geierlehner, A.; Horch, R.E.; Ludolph, I.; Arkudas, A. Intraoperative Blood Flow Analysis of DIEP vs. ms-TRAM Flap Breast Reconstruction Combining Transit-Time Flowmetry and Microvascular Indocyanine Green Angiography. *J. Pers. Med.* **2022**, *12*, 482. https://doi.org/10.3390/ jpm12030482

Academic Editor: Gianluca Franceschini

Received: 27 January 2022 Accepted: 14 March 2022 Published: 16 March 2022

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the sole assessment of arterial flow characteristics, or the use of nowadays outdated technologies [15–19]. This study measures and compares intraoperative arterial and venous blood flow and perfusion characteristics of DIEP and ms-TRAM flaps for breast reconstruction combining Transit-Time Flowmetry (TTFM) and Indocyanine Green Angiography at a microscopic level (mICG-A). TTFM, an ultrasound-based technology for the assessment of vascular blood flow, was originally introduced into clinical practice for cardiac surgery [20,21]. Validation studies showed highly accurate and reproducible measurements which enabled its extension towards other surgical specialties such as vascular surgery and microsurgery [22–24]. The intravenous application of Indocyanine Green in combination with microscope-integrated fluorescence-based video angiography (IR800) and the analysis tool FLOW800 (Carl Zeiss, Oberkochen, Germany) enables the recording, measurement, and assessment of the microvascular patency and blood flow characteristics of vessels just a few millimeters in diameter [25,26]. The assembly of these two state-of-the art technologies is considered a novel approach. We believe that an advanced understanding of their hemodynamic properties will improve the safety of the two most commonly used free flaps for autologous breast reconstruction. This study further aimed to establish normative blood flow and perfusion values as groundwork for the determination of predictive values for postoperative thrombotic events.

### **2. Materials and Methods**

Patients receiving DIEP or ms-TRAM flaps for breast reconstruction were enrolled in this prospective mono-centered clinical study. The study was approved by the Ethical Committee in accordance with the Declaration of Helsinki. Prior to study inclusion, written consent was given by each patient.

#### *2.1. Surgical Technique*

Autologous breast reconstructions were performed by three experienced surgeons. All patients received a standardized computed tomography angiography (CTA) of the abdomen for perforator mapping prior to surgery. Depending on the anatomy of the selected perforators (size, course, and number), the patients included in this study received DIEP or ms-TRAM free flaps for autologous breast reconstruction. Our postoperative anticoagulation regimen usually consists of low-molecular-weight heparin application subcutaneously until full mobilization is achieved. If contraindications for low-molecularweight heparin exist, patients usually receive weight-adjusted unfractionated heparin. Patients suffering from hyperthyroidism, thyroid adenoma or autonomy, and known allergies/hypersensitivity to Indocyanine green or sodium iodide were excluded. The patient body temperature was kept stable by using a warming mattress (37 ◦C) and maintaining the ambient temperature between 20 ◦C and 22 ◦C. All patients received a balanced intraoperative crystalloid volume substitution of, on average, 53 mL/kg (mean: 3780 ± 1710 mL) in order to maintain stable hemodynamic conditions. The average intraoperative blood loss was 140 ± 100 mL. The internal mammary artery (IMA) and vein (IMV) were used as recipient vessels in all cases. Each flap was harvested in a standardized fashion with the inferior epigastric artery and the inferior epigastric vein as vascular pedicle dissected towards their origin at the external iliac artery and vein. Each vascular pedicle consisted of one artery and one vein. DIEP and ms-TRAM flaps with more than one venous anastomosis were excluded from this study. All arterial and venous anastomoses were performed end to end. Arterial anastomoses were hand-sewn with interrupted nylon sutures, whereas all venous anastomoses were performed using a venous coupler device (Synovis Micro Companies Alliance, Inc., Birmingham, AL, USA).

#### *2.2. Transit-Time Flow Measurement (TTFM)*

MiraQ™ Vascular (Medistim ASA, Oslo, Norway) was used for intraoperative blood flow measurements. The probe diameter ranged from 1.5 to 4 mm depending on the vessel size. Blood flow values were recorded for several minutes until a steady curve of blood flow occurred (Figure 1). Arterial and venous blood flow volume measurements were performed at three predefined time points during surgery:


**Figure 1.** Transit-Time Flow Volume Measurement (TTFM) showing a flow volume of 10 mL/min with an Acoustic Coupling Index (ACI) of 73% using a 2 mm probe.

The mean arterial pressure was measured and documented at each measurement time point.

#### *2.3. Microvascular Indocyanine Green Angiography (mICG-A)*

In this clinical study, Indocyanine Green (ICG) was administered as an intravenous bolus (3 mL VERDYE 5 mg/mL) after arterial and venous anastomosis and flap reperfusion. The anastomosed flap pedicle was placed below the microscope (KINEVO 900, Carl Zeiss, Oberkochen, Germany). Recordings of the supplying artery and draining vein started immediately after intravenous ICG application and were continued until the intensity of the ICG markedly decreased in the artery and vein. Intraoperative fluorescence analysis requires the selection of certain regions of interest (ROI). Two ROIs were placed at the flap pedicle, one at the supplying artery, and the other at the draining vein close to the anastomosis, uncovered from any surrounding tissue (Figure 2). FLOW800 measures the intensity of ICG in the regions of interest for a time period and enables the instant visualization of blood flow variations within small vessels. The time between the maximum ICG intensity of arterial inflow and venous outflow is defined as Intrinsic Transit Time (ITT), which is considered as a parameter of blood flow velocity within the flap (Figure 2) [27].

**Figure 2.** (**A**) Microvascular Indocyanine Green Angiography (mICG-A) flow curves in two selected regions of interest (ROI) (green curve: arterial flow, blue curve: venous flow). The spikes are artefacts caused by respiratory movements. (**B**) Delay Map obtained with FLOW800 illustrating both ROIs (green ROI placed at the artery, blue ROI placed at the vein) and picturing the two flow curves. (**C**) Gray-scale map of fluorescence intensity (Intensity Map) illustrating both artery and vein after anastomosis.
