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\begin{document}

\title{Shape-Sensing Robotic Bronchoscopy in the Diagnosis of Pulmonary Lesions
in Children.}



\author[1]{Guillermo Beltran Ale}%
\author[1]{Ryne Simpson}%
\author[1]{Christopher Mertens}%
\author[1]{Elsa Santillana}%
\author[2]{Benjamin Hill}%
\author[3]{Waldermar Carlo}%
\author[1]{Hitesh Batra}%
\affil[1]{University of Alabama at Birmingham}%
\affil[2]{Children’s of Alabama}%
\affil[3]{The University of Alabama at Birmingham Department of Pediatrics}%


\vspace{-1em}



  
  \date{May 19, 2024}


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\selectlanguage{english}
\begin{abstract}
To our knowledge, this is the first reported case of successful
transbronchial biopsy via RB in a 5-year-old patient. The sample
revealed a potential diagnosis, but more importantly, helped rule out an
active infectious process and avoided an open lung biopsy which was
being planned and would have otherwise been necessary to establish a
diagnosis. We believe this technology can be used to increase the
diagnostic yield of flexible bronchoscopy, particularly in the
immunocompromised population as there is already evidence supporting
image-guided bronchoscopy over conventional bronchoscopy in this
population {[}(4){]}(\#ref-0004). A notable limitation to RB is the size
of the available bronchoscopes for robotic platforms (4.5 and 3.5 mm
OD). In children, this may limit the capacity to sample more peripheral
lesions via fine needle aspiration, as more lung tissue (relative to
chest size) may be injured. In our case, the catheter tip was never as
close to the lesion as it has been described in adults
{[}(2){]}(\#ref-0002). As the field of pediatric interventional
pulmonology continues to develop, RB will likely be one of several
options available for safe and high-yield diagnostic procedures.%
\end{abstract}%



\sloppy


\textbf{Clinical Correspondance}

\textbf{Title:}

Shape-Sensing Robotic Bronchoscopy in the Diagnosis of Pulmonary Lesions
in Children.

\textbf{Authors:}

Guillermo Beltran-Ale\textsuperscript{1,2}, Ryne
Simpson\textsuperscript{1,2}, Christopher Mertens\textsuperscript{1,2},
Elsa Santillana\textsuperscript{3,4}, Benjamin Hill\textsuperscript{5},
Waldermar Carlo\textsuperscript{2,6}, Hitesh Batra\textsuperscript{3,4}

\textsuperscript{1}Division of Pediatric Pulmonary and Sleep Medicine,
University of Alabama at Birmingham, Birmingham, Alabama

\textsuperscript{2}Department of Pediatrics, University of Alabama at
Birmingham, Birmingham, Alabama

\textsuperscript{3}Division of Pulmonary, Allergy, and Critical Care
Medicine, University of Alabama at Birmingham, Birmingham, Alabama

\textsuperscript{4}Department of Medicine, University of Alabama at
Birmingham, Birmingham, Alabama

\textsuperscript{5}Department of Pathology, Children's of Alabama,
Birmingham, Alabama

\textsuperscript{6}Division of Pediatric Cardiology, University of
Alabama at Birmingham, Birmingham, Alabama

\textbf{Financial Disclosure:}

The authors declare they have no relevant financial interests.

\textbf{Conflicts of Interest:}

Dr. Hitesh Batra serves as a consultant and proctor for Intuitive.

\textbf{Key Words:}

Robotic Bronchoscopy, Interventional Pulmonology, Children, Navigational
Bronchoscopy

\textbf{Correspondence to:}

Guillermo Beltran Ale, MD

University of Alabama -- Birmingham

Department of Pediatrics, Division of Pulmonary and Sleep Medicine

620 Jarman F. Lowder Building

1600 7\textsuperscript{th} Avenue South

Birmingham, AL 35233

Email: gjbeltranale@uabmc.edu

\textbf{To the Editor,}

Robotic bronchoscopy (RB) is becoming a preferred method for sampling
peripheral pulmonary lesions in adults. RB allows preparation for the
procedure using a planning software and provides direct visualization of
the airways while simultaneously controlling the location of the scope
assisted by a virtual 3-D reconstruction. Accuracy of navigation is
verified with fluoroscopy and/or radial probe ultrasound (rEBUS) during
the procedure (1). In adults, there is growing evidence that RB can
increase diagnostic yield while minimizing complications (2).
Alternative methods include percutaneous CT guided biopsy which lacks
the ability to biopsy multiple lesions and carries a higher risk of
complications, as well as conventional bronchoscopy which is often
unable to maneuver into more peripheral lesions. Published data for RB
report a diagnostic yield of 69 -- 88\% and a 0 - 3.8\% rate of
pneumothorax (3).

We are aware of unpublished experiences using RB in teenagers and
cone-beam CT guided bronchoscopy in younger children. There is
minimal-to-no published data of the use of RB in the latter group. As
one of the available platforms utilizes a scope with a 3.5 mm outer
diameter (OD) it could be used in small children. Here, we present a
case demonstrating the utility of RB in a 5-year-old with peripheral
pulmonary lesions.

\textbf{Case}

A 116 cm, 20.9 kg 5-year-old post orthotopic heart transplant for
dilated cardiomyopathy presented with right-sided peripheral pulmonary
opacities on chest CT. She had previously completed intravenous
antifungal therapy for \emph{Rhinocladiella similis} fungemia acquired
while on left ventricular assist device support. CT revealed the
development of numerous ill-defined, nodular opacities within all lobes
of the right lung and several small areas of calcification in the right
middle and lower lobes (Figure 1). Flexible bronchoscopy with
bronchoalveolar lavage (BAL) was performed, however, broad testing
failed to yield a diagnosis. Oral antifungal therapy was continued with
plans for repeat imaging in 1 month. CT again revealed right-sided
nodules in a similar distribution, but with increased density (-200
versus -450 Hounsfield units). In addition, several left-sided nodules
had developed in the lingula and left upper lobe. Due to the clinical
history and radiographic evolution, tissue biopsy was requested. Because
of the patient's size and peripheral location of the nodules, biopsy
using the Intuitive Ion\textsuperscript{TM} Robotic Bronchoscopy system
was attempted to avoid percutaneous biopsy or video assisted
thoracoscopy.

\textbf{Procedure}

The Ion\textsuperscript{TM} Endoluminal System by Intuitive was used. A
CT with 1.5 mm thick slices was uploaded into the
PlanPoint\textsuperscript{TM} software. After airway segmentation by the
software, target lesions were identified in both the right upper and
lower lobes, pathways were planned and reviewed through a virtual
simulation. The patient was intubated with a 6.0 endotracheal tube
(ETT). A 4.2 mm bronchoscope (Olympus BF-P190\textsuperscript{TM}) was
first used to complete a standard airway examination and aspirate
secretions. The Ion system was then docked to the ETT via a magnetic
adapter and the 3.5mm catheter with the vision probe inside it was
inserted into the ETT. A standard registration including verification of
the main carina and airways in each of the four quadrants was performed.
The catheter was then navigated close to the right lower lobe target
lesion under direct visualization and in accordance with the virtual
navigation path created using the pre-procedure CT scan. Due to the
small size of sub-segmental airways, we could not get closer than 22 mm
from the RUL target nodule, and 32 mm from the RLL target nodule.
However, we chose the RLL target for biopsy as we were able to introduce
the catheter into an airway leading directly to the nodule (Figure 2).
There was no appreciable CT-to-body divergence. The vision probe was
then removed, and a rEBUS probe was inserted, which revealed a
concentric signal. The rEBUS probe was then removed and multiple forceps
biopsies were performed using the Olympus EndoJaw Disposable Biopsy
Forceps with fluoroscopic guidance using a overlay of an image of the
rEBUS probe extended to the distal end of the nodule. After several
pieces of tissue were obtained, a BAL was performed. There were no
immediate complications and a post-operative chest X-ray was
unremarkable without evidence of pneumothorax.

The infectious work up was again negative. The pathology slides showed
benign, distorted/hemorrhagic lung parenchyma with minimal inflammatory
infiltrate, occasional hemosiderin-laden macrophages and several foci of
dystrophic calcification (Figure 1). Due to right-sided unilaterality,
vascular dysfunction was considered but CT angiography, trans-esophageal
echocardiogram, and cardiac catheterization showed normal flow within
the right-sided vessels and anastomosis.

\textbf{Discussion}

To our knowledge, this is the first reported case of successful
transbronchial biopsy via RB in a 5-year-old patient. The sample
revealed a potential diagnosis, but more importantly, helped rule out an
active infectious process and avoided an open lung biopsy which was
being planned and would have otherwise been necessary to establish a
diagnosis. We believe this technology can be used to increase the
diagnostic yield of flexible bronchoscopy, particularly in the
immunocompromised population as there is already evidence supporting
image-guided bronchoscopy over conventional bronchoscopy in this
population (4). A notable limitation to RB is the size of the available
bronchoscopes for robotic platforms (4.5 and 3.5 mm OD). In children,
this may limit the capacity to sample more peripheral lesions via fine
needle aspiration, as more lung tissue (relative to chest size) may be
injured. In our case, the catheter tip was never as close to the lesion
as it has been described in adults (2). As the field of pediatric
interventional pulmonology continues to develop, RB will likely be one
of several options available for safe and high-yield diagnostic
procedures.

The patient was considered to have metastatic pulmonary calcifications.
These lesions are benign, and have been reported to self-resolve as
there are no available treatment options (5). This entity has been
described after infectious process, associated with renal failure and
severe calcium or phosphorus abnormalities (5) and as isolated findings
after liver or heart transplants (5). Follow-up imaging continues to
demonstrate the same lesions without evidence of progression, and the
patient remained asymptomatic.

\textbf{References}

1. Lin J, Ost DE. Robotic bronchoscopy for peripheral pulmonary lesions:
a convergence of technologies. Curr Opin Pulm Med. 2021;27(4):229-39.

2. Chen AC, Pastis NJ, Jr., Mahajan AK, Khandhar SJ, Simoff MJ, Machuzak
MS, et al. Robotic Bronchoscopy for Peripheral Pulmonary Lesions: A
Multicenter Pilot and Feasibility Study (BENEFIT). Chest.
2021;159(2):845-52.

3. Folch E, Mittal A, Oberg C. Robotic bronchoscopy and future
directions of interventional pulmonology. Curr Opin Pulm Med.
2022;28(1):37-44.

4. Bouso JM, Yendur O, Hysinger E, Planet PJ, Haas A, Goldfarb S, et al.
Endobronchial Ultrasound-guided Biopsy Is Feasible, Safe, and Improves
Diagnostic Yields in Immunocompromised Children. Am J Respir Crit Care
Med. 2020;201(3):384-6.

5. AlNuaimi D, ElKaissi M, Wahla A, Shafiq I, Abdulghaffar S. Metastatic
pulmonary calcifications postcardiac transplant in a 15-year-old
patient: A case report and review of literature. Radiol Case Rep.
2020;15(10):1978-82.

\textbf{Figure 1: Chest CT showing parenchymal opacities in the right
middle lobe and right lower lobe. Lesions in the right lower lobe were
peripheral and had not increased in volume but changed density within 4
weeks. Trans-bronchial lung biopsy slide showing alveolar cells and 1
center of dystrophic calcification.}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 2: RB platform screen. In the upper portion the virtual
navigation path with lesions colored dark green and pleural space
colored purple. Below this, an image indicating the distance from the
tip of the scope (bright green) to the identified lesions (light blue
oval). In the lower portion a fluoroscopic image showing both the
forceps and the rEBUS probe overlay image and on the left side the
virtual bronchoscopy view and rEBUS signal.}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\selectlanguage{english}
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