Fig. 24.9  Planning procedure with inspiration and expiration CT scan

Procedure

The procedure of SPiNView is performed in the following steps

Planning

This phase is similar to the iLogic(R) system. vPads tracker is placed on the patient chest prior to the CT scan. It contains electromagnetic sensors which enable automatic registration and respiratory motion tracking. The system uses both inspiration and expiration CT images of the patients’ airways to plan the route to the lesion. The targeted SPN is marked and the software then creates a 3D roadmap of targeted lesions. The SPiNView software uses an expiration CT scan to match a patient's respiration state. Then, the pathway is transferred and is uploaded for the navigation phase.

Navigation

A SPiNView bronchoscopy catheter is available with steerability. The SPiNView system can automatically perform registration without bronchoscopist effort. During this phase, the electromagnetic generator tracks the Always-On Tip Tracked instrument as it advances toward the

lesion in the lung. The view peripheral catheter provides digital laser optics which has built in electromagnetic sensors. It provides guidance throughout the procedure.

Biopsy

The targeted lesion is reached by a tip tracked instrument. The bronchoscopist performs biopsies of the lesion while the instrument is left in place. The tip tracked steerable working channels, tip tracked aspiration needles and navigation guide wires that enable ultrathin bronchoscopes to be navigated to the peripheral regions of the lung all with clear virtual visualization. The SPinFleX needle is made with nitinol, making it possible to turn 180° and get to dif cult lesions in the lungs. The bronchoscopist always knows where the sensor is within the body while sampling. The con rmation by fuoroscopic image is optional.

Diagnostic Yield and Results of EMN-­

Guided TBBx

Early studies were primarily retrospective, single-­center case series which varied signi - cantly in their study designs and outcomes (Fig. 24.10).

In 2003, Schwarz et al. [21] performed therst animal trial to determine the practicality, accuracy and safety of the real time EMN in locating peripheral lung lesions in a swine model. The study proved that EMN was accurate when added to the standard bronchoscopy to assist in reaching peripheral lung lesions. The average procedure time was 2 min for the mapping component and 5 min for the navigation component. Arti cially created lung lesions were sampled without dif culty or complications, using conventional biopsy tools.

Becker et al. [11] published results of a pilot study in humans. They obtained biopsies of the peripheral lesions under the guidance of EMN in 30 adults. Evaluation was possible in 29 patients; de nitive diagnosis was established in 20 patients (69%). EMN added a mean of 7.3 min of time to the bronchoscopy procedure. There was one

pneumothorax requiring chest tube insertion. They concluded that EMN is feasible and safe as an aid to obtaining biopsies of peripheral lung lesions.

In 2005, a second electromagnetic navigation system, the Aurora electromagnetic tracking device (Northern Digital, Waterloo, ON, Canada) was described by Hautmann et al. [22]. The prospective evaluation of an EMN system for the diagnosis of peripheral in ltrates or solitary lesions was conducted in 16 patients. In all of the pulmonary in ltrates and solitary lesions, the navigation system was able to guide the sensor tip to the center of the lesion, despite some being undetectable by fuoroscopy. All the lesions were reached by EMN and tissue was sampled successfully for the histological examination. Overall, EMN was well-tolerated and proved to be safe and useful in localizing small and fuoroscopically invisible lung lesions with an acceptable level of accuracy.

The rst large-scale prospective clinical study was conducted by Gildea et al. [13] to determine the ability of EMN to sample peripheral lung lesions and mediastinal lymph nodes. Sixty subjects were enrolled and the diagnostic yield was 74% for the peripheral lesions and 100% for mediastinal lymph nodes. A diagnosis was obtained in 80.3% of bronchoscopic procedures

with EMN. The lesions were accessed in all subjects. Two patients developed pneumothorax (3.5%). There was no signi cant relationship between diagnosis and size or the location of the peripheral lesions or lymph nodes.

The other prospective studies were undertaken by Makris et al. and Eberhardt et al. [23–27] to determine the yield of EMN without using fuoroscopy in the diagnosis of peripheral lung lesions. The diagnostic yield in these studies ranged from 59% to 87.5%. In this study, the diagnostic yield was lower for the upper lobe lesions probably due to the acute angle of the corresponding bronchus having a sharper angle in the bronchial tree and it may be challenging to navigate [26]. These studies concluded that EMN can be used as a stand-alone procedure (without fuoroscopy) without compromising diagnostic yield or increasing the risk of pneumothorax.

It has also been established by a prospective, randomized trial that combination of EBUS (Endobronchial Ultrasound) and EMN improves the diagnostic yield of FB in peripheral lung lesions without compromising safety [25]. In this particular study, 72% of all 118 patients recruited had a positive diagnostic yield via FB. Combined EBUS/EMN had a signi cantly higher diagnostic yield of 88% compared to that of EBUS (69%) and EMN (59%) alone. In this study, the diagnos-

tic yield from the lower lobes was signi cantly lower which could be attributed to navigation error. Navigation in lower lobes may be more challenging due to diaphragmatic movement during breathing. The planning data are based on CT images acquired in a single breath hold and cannot compensate for breathing movements. The improved yield of the joint procedure ascribed to combining the ability of EBUS to directly visualize the peripheral lung lesions with the precise navigation capabilities of EMN. The overall pneumothorax rate was 6% (7 patients) and 6.3% (5 patients) when EMN was used. Four of the 7 patients required a chest tube placement.Although this combination provides a higher diagnostic yield compared to either one of them alone, the issues of cost and training need to be addressed.

The utility of Rapid On-Site Evaluation (ROSE) along with EMN has been demonstrated in a retrospective, single-center study was carried out to evaluate the diagnostic yield of bronchoscopy, guided by EMN plus the ROSE of the cytology specimens [28]. Of 248 subjects, 65% received a de nitive malignant or non-malignant diagnosis on the day of the procedure. During the follow-up 12 patients (5%) were con rmed to be free of malignancy and 8 patients (3%) were con-rmed as having malignant disease. Sixty-seven patients (27%) were lost for follow-up. The diagnostic yield probably ranged between 70% and 97% based upon the assumptions made regarding the outcome of the cases that had an inconclusive diagnosis on the day of the procedure. In this particular study, pneumothorax was encountered in three patients and a few other minor complications yet none of the latter were related to the use of EMN. It was concluded that combination of EMN and ROSE can provide a better diagnostic yield in patients with a peripheral lung lesion.

The combination of EMN, PET-CT, and ROSE were further studied for the routine diagnostic workup of peripheral lung lesions [29]. EMN was performed in 13 subjects, where the PET-CT scans were the part of the diagnostic workup. In 76.9% of the patients EMN resulted with a de nitive diagnosis. No pneumothorax or any other complications related to the procedure were encountered. Patients with peripheral lung lesions, EMN in

combination with ROSE and prior PET-CT, were shown to be safe and highly effective.

Catheter aspiration was compared to the traditional forceps biopsy technique of small pulmonary nodules suspicious for malignancy using EMN [27]. Both tools were used to sample suspicious malignant lesions in 53 patients. EBUS was used to verify the accuracy of target lesions as well. Diagnosis was obtained in 75.5%. Sampling by catheter aspiration was associated with a higher diagnostic yield than sampling by forceps biopsy alone (p = 0.035). When rp-EBUS veri ed the lesion location after navigation, the diagnostic yield was 93% compared to only 48% when lesion location was not con rmed [28]. There was 1 pneumothorax, treated conservatively.

In meta-analysis, including 11 ENB studies, the weight diagnostic yield of ENB was at 67% [30]. Nine of these studies utilized ENB alone without other diagnostic modalities such as radial probe EBUS. Another meta-analysis and systematic review of ENB included 1033 lung nodules which showed the overall de nite diagnostic yield of 64.9%. Several variables included size of the nodule, location in lower lobe, bronchus sign, average ducial target registration error (AFTRE), visualization of nodule with radial-­probe EBUS, and catheter suction technique were reported to be signi cant predictors in univariate analysis. However, only bronchus sign was reported as a signi cant predicting factor in multivariate analysis [31]. Meanwhile, the use of General anesthesia and rapid onsite cytologic evaluation were associated with better diagnostic yield. However, there were only four trials using these techniques, precluding nal conclusions. The large AQuIRE registry included 581 patients and showed diagnostic yield of 38.5% when the use of EMN as single modality, 57% with rp-­EBUS alone. The combination of EMN and rp-­EBUS provides a diagnostic yield of 47.1% [32]. Recently, the EMN-SD platform was studied in a large, prospective, multicenter study (NAVIGATE). This study included over 1000 patients from 29 centers in the United States. Almost half of all lesions (49.1%) were less than 20 mm in size. Successful navigation and tissue acquisition

rate was 94.4%, the 12-month diagnostic yield was 72.9%, and the 12-month sensitivity for malignancy was 68.8% [33]. Overall complication rates were low: pneumothorax rate of 4.3%, serious bleeding rate of 1.5%, and respiratory failure rate of 0.4%. Recently, NAVIGATE study reported prospective 24-month follow-up from the same cohort. The 24-month diagnostic yield was 67.8% and the pneumothorax rate was 4.7% [34]. To date, NAVIGATE study is the largest published EMN-SD study. The combination of staging EBUS along with EMN-guided biopsy of peripheral lesions is considered as standard of care for minimally invasive staging of lung cancer. The ongoing study is designed to evaluate the diagnostic yield of a staged procedure using EBUS, ENB, and EMN-TTNA for the diagnosis of SPN [35].

[36]. The pilot study in 24 patients underwent both EMN-guided TBBx and ETTNA. The diagnostic yield for ETTNA alone was 83% and increased to 87% when ETTNA was combined with navigational bronchoscopy. With the combination with EBUS for complete staging, ETTNA and NB had a diagnostic yield of 92%. There was no major bleeding. However, there was 21% risk of pneumothorax of which only two (from ve) patients required drainage. The second study enrolled 102 patients into the study. Twenty cases, 22% (20/92) were converted to the percutaneous transthoracic core needle biopsy. The diagnostic yield rate was raised approximately 20% by concurrent percutaneous transthoracic needle biopsy. There is 10% risk of pneumothorax with the need for chest tube drainage (Fig. 24.11) [37].

Localizing non-visible and non-palpable peripheral lung nodules during thoracoscopic resection can be challenging. A variety of techniques have been described to mark the pleural surface in the vicinity of these nodules to guide the surgeon. The use of EMN-guided pleural ­tattoo injection with methylene blue or indigo carmine to assist video-assisted thoracoscopic surgical (VATS) wedge resection of pulmonary nodules has been reported in a few studies [38–40].

The use of EMN for subpleural ducial markers placement was reported in a few studies. This was followed by successful VATS wedge resection during the same procedure. Fiducial placement of an average of three markers led to an adequate retention rate to allow for successful treatment of lung cancer in patients undergoing stereotactic radiation. There are several brands ofducial markers available in the market which have different retention rates. The VortX coilducial had a retention rate of 96.7% [41, 42].

In external beam radiation of lung cancer, the metallic ducials are usually implanted transcutaneously under CT or fuoroscopic guidance. Kupelian et al. compared this method to transbronchial placement of metallic ducials using EMN [43]. Eight of the 15 patients who had the implantation transcutaneously developed pneumothorax and 6 of them required a chest tube. No pneumothorax was observed in the 8 patients who underwent the placement using EMN bronchoscopy. The implanted markers were stable within the tumors throughout the treatment duration regardless of implantation method.

Stereotactic body radiation therapy (SBRT) is a treatment option for patients who are medically suitable to undergo surgical lung tumor resection [44]. This technology has been complemented by more targeted chemotherapeutic regimens, novel methods of administering more accurate and more concentrated doses of radiation therapy, and innovative local excisional methods. For a precise tumor ablation, SBRT requires ducial marker placement in or near the tumor. In the past it was being carried out via transthoracic route under CT guidance with an obviously high risk of pneumothorax. In a single study a total of 39

ducial markers were successfully deployed in 8 of 9 patients using EMN guidance without any complication [45]. This nding supports the notion that EMN can be used to deploy ducial markers for SBRT, safely and accurately.

A recent study described the use of coil-springducial markers in inoperable patients with isolated lung tumors planned for CyberKnife treatment [46]. A total of 52 consecutive patients underwent ducial markers placement using EMN bronchoscopy. Of these, 4 patients received 17 linear ducial markers and 49 patients with 56 tumors received 217 coil-spring ducial markers. A total of 234 ducial markers were successfully deployed in 52 patients with 60 tumors. At CyberKnife planning, 8 (47%) of 17 linear ducial markers and 215 (99%) of 217 coil-springducial markers were still in place (p = 0.0001). Of the 4 patients with linear ducial markers, 2 required additional ducial placements while none of the patients with coil ducial markers required additional procedures. Three pneumothoraces (5.8%) were encountered (2 of them needed a chest tube). The bronchoscopy procedures were performed under moderate sedation in an outpatient bronchoscopy suite.

A novel EMN system that provides tracking for percutaneous procedures has been introduced to aid radiologists in their different pulmonary interventions [47, 48]. The tracking is performed percutaneously without using bronchoscopy. This system did not show any bene t in terms of reducing CT fuoroscopy time or radiation dose when compared to the traditional percutaneous CT fuoroscopy-guided-biopsy of small lung lesions [49]. This EMN system was also evaluated to determine its potential to reduce the number of skin punctures and instrument adjustments during CT-guided percutaneous ablation and biopsy of lung nodules [47]. This early experience suggested a low number of skin-puncture and instrument adjustments when using the system.

In terms of Radiofrequency-induced Tissue ablation (RFA), this approach offers a minimally invasive modality [48, 49]. A small prospective trial for RFA demonstrated the early histopathological changes following RFA in a surgical set-