Exploring optimal settings for safe and effective thulium fiber laser lithotripsy in a kidney model

Abstract

Objectives:

To explore the optimal laser settings and treatment strategies for Thulium Fiber Laser (TFL) lithotripsy with the highest treatment efficiency, lowest thermal injury risk, and shortest procedure time.

Materials and Methods:

An in-vitro kidney model was utilized to assess the efficacy of TFL lithotripsy. Stone ablation experiments were performed on BegoStone phantoms at different combinations of pulse energy (E_P) and frequency (F) to determine the optimal settings. Temperature changes and thermal injury risks were monitored using embedded thermocouples. Experiments were also performed on calcium oxalate monohydrate (COM) stones to validate the optimal settings.

Results:

High E_P/low F settings demonstrated superior treatment efficiency compared to low E_P/high F settings under the same power. Specifically, the optimal settings of 0.8 J/12 Hz resulted in a two-fold increase in treatment efficiency, 39% reduction in energy expenditure per unit of ablated stone mass, 35% reduction in residual fragments, and 36% reduction in total procedure time compared to the 0.2 J/50 Hz for COM stones. Thermal injury risk assessment indicated that 10 W settings with high E_P/low F combinations remained below the threshold for tissue injury, while higher power settings (> 10 W) consistently exceeded the safety threshold.

Conclusions:

Our findings suggest that high E_P/low F settings, such as 0.8 J/12 Hz, are optimal for TFL lithotripsy in the treatment of COM stones. These settings demonstrated significantly improved treatment efficiency with reduced residual fragments compared to conventional settings while keeping the thermal dose below the injury threshold. This study highlights the importance of using high E_P/low F in low power settings, which maximize treatment efficiency and minimizes potential thermal injury. Further studies are warranted to determine the optimal settings of TFL for treating kidney stones with different compositions.

Introduction

Urolithiasis impacts approximately 10.6% of men and 7.1% of women in the United States [1]. Ureteroscopy (URS), traditionally utilizing a Holmium (Ho): Yttrium Aluminum Garnet (YAG) laser, is the gold standard laser for treating urolithiasis during laser lithotripsy (LL) [2]. The Thulium Fiber Laser (TFL) is an evolving competitor for LL, which presents both opportunities and challenges for urologists as they strive to improve treatment efficiency for urolithiasis.

Several in-vitro studies have highlighted the advantages of TFL over Ho: YAG laser [1]. These advantages include a lower stone damage threshold, higher ablation efficiency [3], reduced procedure time [4, 5], and a smaller retropulsion effect [6], primarily due to the long pulse duration combined with a low peak power of the TFL (Table S1). In addition, at a wavelength of 1940 nm, the TFL has a significantly higher optical absorption in water than the Ho: YAG laser (2120 nm) [7]. This increased absorption in water contributes to improved thermal ablation of the stone, however, it may also lead to rapid temperature rises when treating impacted stones in the ureter leading to thermal injury and eventual stricture formation [8].

The TFL offers a wide range of settings, including pulse energies from 0.025 J to 6 J and pulse frequencies from 1 Hz to 2,400 Hz. Despite numerous clinical trials and in-vitro studies, the optimal settings have not yet been established [4, 9, 10]. Based on empirical experience from Ho: YAG lasers, some urologists advocate the use of low E_P and high F combinations to improve dusting efficiency and treatment outcomes [11]. Consequently, the dusting settings of TFL have been significantly stretched beyond the established Ho: YAG laser settings [12] towards lower E_P and higher F domain (see Fig. 1a). Furthermore, the safety profile of TFL warrants a comprehensive evaluation to reduce the risk of kidney and ureteral injury-related outcomes.

Fig. 1.

(a) Comparison of clinical pre-settings used for TFL (purple) across various studies [9, 10, 21] with the in vitro test results (orange: bench-top experiments; green: kidney phantom experiments) in this work, demonstrating distinct differences in the parameter space (EP vs. F) of the optimal settings for producing the best stone ablation outcome. Here blue zone represents Ho: YAG clinical pre-settings. (b) Anatomical kidney phantom model and the location of six - thermocouples (T1 – T6) with respect to the stone treatment location. One additional thermocouple was placed in the water tank to monitor the baseline temperature. (c) Comparative analysis of TFL treatment efficiency (mg/s) and (d) laser energy efficiency (J/mg) for BegoStone samples.

To address these fundamental challenges, we performed a series of experiments to explore the optimal settings and treatment strategies using BegoStone phantoms and COM stones in a recently developed in-vitro anatomically realistic kidney model [13]. The aim of our study is to identify the most effective settings for the most favorable outcomes, encompassing the highest treatment efficiency, lowest thermal injury risk and shortest procedure time using the burgeoning TFL technology for urolithiasis treatment.

Materials and Methods

Artificial Stone and Kidney Model Preparation.

Experiments were performed in an anatomically realistic 3D kidney model (Fig. 1b) constructed using 3D images from human CT imaging studies employing a synthetic ballistic gel (Gelatin #1, Humimic Medical, SC, USA). The acoustic, mechanical, and thermal properties resembled those of human renal tissue [13]. BegoStone phantoms were prepared as 6 × 6 mm cylinders (~250 mg, BEGO™ USA, Lincoln, RI) with a powder-to-water ratio of 5:2. The phantoms were soaked in water for 24 hours before laser treatment [14] using the experimental setup shown in Fig. S1.

Laser Treatment.

An IPG TFL system (TFL-50/500-QCW-AC, IPG Photonics, Oxford, MA) was used. A flexible ureteroscope (Dornier AXIS^™, 3.6 F working channel, Munich, Germany) with a 200 μm core-diameter laser fiber (NA = 0.22) was used by an experienced endourology fellow targeting the stone in an upper calyx (volume = 1.63 cm³). For each laser setting, five measurements were taken (n =5). Each experimental trial was timed for the laser on time and laser off time until the stone was no longer able to be adequately dusted into a smaller size. We applied continuous laser energy until treatment completion or until significant vision impairment occurred due to a snowstorm of dust [15]. To explore the optimal settings, different combinations of E_P (from 0.2 to 1.5 J) and F (from 6 to 150 Hz), covering a power range of 10 W to 30 W (see Table 1), were selected based on our preliminary bench-top experiments [16, 17]. During treatment, a short pulse profile is preferred over a long pulse profile, as shorter pulse settings previously demonstrated superior ablation outcomes even at higher pulse energies (Ep ≥ 1 J) [16].

Table 1.

Summary of the TFL parameters employed during the LL experiments, including single pulse energy (E_p), frequency (F), power (P), and pulse duration (τ)

Power [P (W)]	Pulse Energy [Ep (J)]	Frequency [F (Hz)]	Pulse Duration [τ (μS)]
10	0.2	50	304
10	0.8	12	1334
10	1.5	6	2544
20	0.2	100	304
20	1.0	20	1685
20	1.5	12	2544
24	0.4	60	651
30	0.2	150	304
30	0.5	60	831
30	1.0	30	1685
30	1.5	20	2544

Thermal Injury Risk Assessment.

To ensure thermally safe LL treatment and monitor temperature changes, six PFA K-type thermocouples (OMEGA, Norwalk, CT, USA) were embedded at discrete locations near the tissue boundary of the upper pole calyx (Fig. 1b). Room temperature irrigation with a controlled flow rate of 40 ml/min [18, 19] was employed using a peristaltic pump (Masterflex^®) to ensure visibility during the LL procedure. To assess the potential risk of thermal injury, the thermal dose [20], evaluated by the cumulative equivalent minutes at 43 °C (CEM43°C), was calculated using:

$$\text{CEM}43°\text{C}={\int }_0^{{\text{t}}_{\text{final}}}{\text{R}}^{43}-{\left(\text{ΔT}+37\right)}_{\text{dt}}$$

where R is 0.25 for T < 43 °C and 0.5 for T ≥ 43 °C.

Validation using Human Stones Treated in the Kidney Model.

Based on the results from the BegoStone experiments, we further conducted the TFL treatment on calcium oxalate monohydrate (COM) stones within the kidney model. Specifically, we compared the treatment outcomes produced at a 10 W power level by two distinct settings: 0.2 J/50 Hz and 0.8 J/12 Each separate experimental procedure was recorded on video to facilitate the offline analysis of various treatment outcomes, including procedure time, laser on/off time, laser-stone interaction, and vision quality. After treatment, the remaining stone fragments were retrieved, air-dried, and sequentially sieved to quantify treatment efficiency. Statistical analysis was conducted using Student’s t-test, considering a p-value < 0.05 as statistically significant.

Results

We conducted the Shapiro-Wilk test to assess the normality for all E_P/F settings, and in each sample test. The results were found to be statistically insignificant. This indicates that the assumption of normality is not violated, and, consequently, the use of the t-test is appropriate for the comparisons. Furthermore, we utilized the Wilcoxon rank sum test to validate our findings, and the test significances align consistently with the t-test results. Given the small sample size of 5 in each group and the fact that for each comparison, the minimum measurement in one group exceeds the maximum in the other group, the p-value (solely determined by the rankings of measurements) consistently equals 0.009.

Assessment of BegoStone Ablation Outcomes

Figs. 1c and 1d compare the treatment efficiency (mg/s) and laser energy utilization efficiency (J/mg) for BegoStone treatment (stone residual ≤ 2 mm). At the same power level, our results demonstrate that the treatment efficiency [Median, Interquartile range (IQR)] of the TFL significantly increased with increasing E_P (p = 0.009), as evidenced by the 28% (in terms of median) increase in treatment efficiency from 0.2 J/50 Hz [0.40 (IQR 0.35–0.40) mg/s] to 0.8 J/12 Hz [0.51 (IQR 0.49–0.55) mg/s] setting (Fig. 1c). In comparison, there is only a 16% increase in treatment efficiency from 0.8 J/12 Hz to 1.5 J/6 Hz [0.59 (IQR 0.53–0.62) mg/s] setting.

Furthermore, in terms of laser energy utilization efficiency (J/mg), as shown in Fig. 1d, about 38% less laser energy (in terms of median) is required to ablate a unit stone mass at either 0.8 J/12 Hz [12.22 (IQR 12.20–12.63) J/mg] or 1.5 J/6 Hz [13 (IQR 12.37–14.27) J/mg] compared to the counterpart at 0.2 J/50 Hz [20.7 (IQR 20.43–21.20) J/mg, p = 0.009 for both comparisons]. Moreover, the 0.8 J/12 Hz (10 W) setting outperforms the 0.2 J/100 Hz (20 W) setting with a 19% higher (median increased from 0.43 (IQR 0.39–0.46) to 0.51 mg/s) treatment efficiency (p = 0.009) and a 66% reduction (median reduced from 36.3 (IQR 33.22–38.09) to 12.2 J/mg) in energy usage (p = 0.009) for stone ablation.

Evaluation of Thermal Injury Risk

The thermocouple measurements revealed a distinct temperature pattern under different E_P/F settings, characterized by a rapid initial temperature increase within 1 to 2 minutes, followed by a stable plateau phase until the laser was turned off (Figs. 2a-2c).

Fig. 2.

Temperature rise profile during the LL treatment of BegoStone, based on TFL, for (a) 10W, (b) 20W and (c) 30W. (d) Accumulated thermal dose produced at different EP/F combinations and power levels settings (see Table 1) in the upper calyx of the anatomical kidney phantom model, considering temperature thresholds and corresponding injury probabilities (Refer – Fig. 1 b for the location of thermocouples T1 – T6). Note that when the cumulative exposure time at or above 43°C exceeds 120 minutes, there is a higher potential for significant tissue damage or adverse effects.

Notably, treatments at 20 W and 30 W exceeded the safety threshold of Δ5 °C [22], with average maximum temperature rise values of 9.66 (standard deviation 4.98) °C and 19.69 (standard deviation 14.27) °C, respectively. In contrast, treatments at 10 W consistently remained below the thermal injury threshold, with an average maximum temperature rise of 4.50 (standard deviation 2.57) °C (p < 0.05). The 0.8 J/12 Hz setting had an average maximum temperature rise of 4.44 (standard deviation 1.77) °C, while 0.2 J/100 Hz had a corresponding temperature rise of 9.75 (standard deviation 3.84) °C. Fig. 2d shows the maximum thermal dose variation for the selected E_P/ F combinations within the power levels of 10 W-30 W. Thermal dose calculated for all E_P/F combinations and at all thermocouple locations (T1 – T6) are shown in Fig. S3a.

Treatment Outcomes with COM Stones

In Table 2, the newly identified optimal TFL settings of 0.8 J/12 Hz for COM stones demonstrate superior treatment outcomes, including a two-fold increase in treatment efficiency, a 39% reduction in energy expenditure per unit of ablated stone mass, and a 35% reduction in residual fragments (size >0.25 mm, as shown in Fig. 3a and b), compared to commonly used 0.2 J/50 Hz pre-settings in clinical LL [10]. Moreover, the 0.8 J/12 Hz setting resulted in a notable 36% reduction in total procedure time and a 21% decrease in laser-on time. Similar to BegoStone phantom experiments, the thermal dose values for the 10 W settings remain below the thermal injury threshold for COM stones, as well (see Table 2). The accumulated thermal dose is lower at 0.8 J/12 Hz compared to 0.2 J/50 Hz. Furthermore, the high E_P/low F setting yielded smaller fragmentation sizes of COM stones, and a higher proportion of fragments were characterized as fine dust (<0.25mm) (Fig. 3c). A thorough examination of the recorded videos revealed distinctions between the two settings. At 0.2 J/50 Hz (Fig. 3d), vision-impairing snowstorm-like dust occurred frequently and persisted for approximately 15 seconds. Conversely, at 0.8 J/12 Hz (Fig. 3e), short-duration spark lighting (~ 2 seconds) was more prevalent, with no char formation based on visual examination of residual fragments. These short sparks generate large-sized stone fragments, as highlighted at 120.94 seconds in Fig. 3e. The scanning speed of the fiber tip, estimated from Figs. 3d and 3e, ranges between 2.2 and 3.4 mm/s, consistent with prior studies [23].

Table 2:

Comparison between treatment outcomes for different TFL settings at high energy/ low frequency combination with low energy/high frequency for COM stone

Treatment outcomes	Ep = 0.2 J, F = 50 Hz	Ep = 0.8 J, F = 12 Hz	p-value	Observations (0.8 J/12 Hz)
	Median [Interquartile range, IQR] (n = 4)
Initial stone mass (mq)	245 [IQR (233–260)]	274 [IQR (256–290)]	0.30	Comparable
Procedure time (S)	322 [IQR (282–360)]	205 [IQR (187–222)]	<0.01	36 % less
Laser-on time [Ablation time] (S)	210 [IQR (190–247)]	170 [IQR (151–186)]	0.10	21 % less
Fraqment mass / Initial mass (%)	37 [IQR (35–40)]	24 [IQR (21–26)]	0.001	35 % less fraqments
Treatment efficiency (mq/s)	0.49 [IQR (0.46–0.54)]	0.98 [IQR (0.96–1.05)]	<0.001	2.03 times faster
Laser enerqy efficiency (J/mq)	13.91 [IQR (12.70–16.54)]	8.44 [IQR (7.89–8.55)]	0.001	0.61 times less enerqy expenditure
Average thermal dose [CEM43°C]	4.21 [IQR (0.23–8.43)]	0.063 [IQR (0.056–0.803)]	0.237	Thermally safe

Fig. 3.

COM stone samples (before the treatment and residual fragments after the treatment) at (a) 0.2 J/50 Hz and (b) 0.8 J/12 Hz, respectively. (c) Fragment size distribution outcome for COM stone during LL along with median values. (d) Ureteroscope view at 0.2 J/50 Hz and (e) at 0.8 J/12 Hz highlighting the features of TFL treatment of COM stones in the kidney model.

Discussion

This study evaluates the optimal settings of TFL for safe and efficient kidney stone treatment using a 3D kidney model. Traditional Ho: YAG laser settings utilize low E_P and high F to decrease the retropulsion effect on stone ablation [24], improve ablation rates and optimize treatment efficiency [3]. The TFL fiber functional energy delivery occurs over a longer pulse duration (~1400 μs at 0.8 J), which can reduce the retropulsion effect, even at higher ablation energies [25]. Our research explores high E_P settings with TFL leveraging its potential in reduced retropulsion, which is distinctly different from the practices for stone dusting utilizing Ho: YAG lasers. To our knowledge, this is the first study demonstrating the superiority of high E_P/low F settings over other clinical settings in an anatomically realistic kidney model for the complete dusting of renal stones.

Our investigation revealed that high E_P/low F settings (0.8 J/12 Hz) outperformed conventional low E_P/high F settings, such as 0.2 J/50 Hz (10 W) and 0.2 J/100 Hz (20 W). Increasing power and E_P significantly enhanced the treatment efficiency, possibly due to more laser pulses delivered to the stone with increased energy deposition per second. This can result in higher thermal ablation, as well as enhanced cavitation-induced damage. However, exceeding 10 W leads to higher fluid temperature, necessitating careful irrigation flow management during LL. Higher flow rates could help mitigate the rapid temperature rise [18]; on the contrary, the higher flow may also cause complications, such as high intrapelvic backpressure [26], potentially leading to sepsis in at-risk patients [22]. Conversely, lower flow rates might risk elevating intraurethral fluid temperature and causing renal injuries [27]. Therefore, during the experiments, we maintained a flow rate of 40 ml/min to prevent heat accumulation and complications [8, 19].

Tissue damage escalates exponentially above ~ 43 °C due to protein denaturation [20], leaving a narrow safety margin of approximately Δ5 °C (Δ5 K) for the safe execution of lithotripsy, assuming a body or irrigation fluid temperature of 37°C [22]. At high power (>10 W), the temperature exceeded the Δ5 °C threshold within 60 seconds in the upper calyx, consistent with reports of thermal damage and stricture during TFL ureteroscopy [8]. At the onset of treatment, the temperature rise was rapid when using low E_P/high F (short pulse duration) settings compared to high E_P/low F (long pulse duration) settings. However, as the treatment progresses, these temperature values converge or may even cross each other. This may be attributed to the progress of stone ablation and/or movement of the fiber tip in relation to the location of the thermocouple.

The calculated thermal dose (CEM43°C) value exceeded the tissue injury threshold for settings > 10 W. This raises concerns regarding high-power settings and the clinical potential for thermal injury. As observed, low E_P/high F settings (0.2 J/100 Hz and 0.2 J/150 Hz) exhibited a rapid initial increase in the thermal dose, plateauing at lower values due to higher energy delivery frequency (see Fig. 2d and Fig. S4). On the contrary, high E_P/low F settings (1 J/20 Hz and 1 J/30 Hz) allowed gradual temperature rise, resulting in higher thermal dose accumulation.

Low power settings (10 W), even with high E_P/low F combinations, remained below the thermal injury threshold, offering a safe option for stone ablation. Our results ultimately converge towards an optimal setting at 0.8 J/12 Hz, which had the lowest CEM43°C value with the highest treatment efficiency among the three thermally safe settings: 0.8 J/12 Hz, 0.2 J/50 Hz, and 0.2 J/100 Hz. Inhomogeneity of temperature rises and thermal dose change may result from the intricate laser energy distribution in the treatment zone, influenced by tissue absorption, scattering, heat dissipation coefficients, and stone motion. Measuring CEM43°C with a thermocouple placed 5 mm from the ureteroscope tip (TScope) may not consistently capture the maximum value of thermal dose around the treated stone (Fig. S3b). Addressing this concern will be essential for precise temperature monitoring during stone ablation in clinical LL.

Unlike previous in-vitro studies [8, 18], where the laser was activated for a fixed duration (e.g., 60 seconds) regardless of the selected E_P/F combinations, our experiments replicated an entire LL procedure, thus providing more clinically relevant insights.

The treatment outcomes for COM stones reaffirmed the superiority of high E_P/low F settings, potentially outperforming conventional stone dusting settings. Additionally, COM stones exhibited higher treatment and energy efficiencies, along with elevated thermal dose values, compared to BegoStone phantoms. The CEM43°C in BegoStone initially increased more rapidly than in COM, as shown in Fig. S4. However, as the experimental procedure concludes, the COM stones exhibited a higher thermal dose and maximum temperature rise [28]. This can likely be attributed to the difference in melting temperature (T_m), where the T_m of COM (T_m = 206 °C) is lower than that of BegoStone (T_m = 1449 °C), causing the remaining energy after stone ablation to be transferred to the surrounding fluid. Nonetheless, factors such as absorption and scattering coefficients of different stone materials, as well as whether the interaction between the laser and stone is exothermic or not, may also play a role. These observations underscore the critical importance of empirically exploring a novel parameter regime to optimize the therapeutic efficacy of TFL in kidney stone management. It has also been noticed that at high E_P/low F settings, the ablation of COM stones into smaller fragments by TFL is facilitated, resulting in fewer basketing passes and simplified URS maneuvers [29].

Notably, exposing COM stones to a high E_P setting (0.8 J/12 Hz) resulted in the emission of sparks. These sparks could originate from plasma formation due to enhanced laser absorption [30] or from the interaction between stone debris and laser light within cavitation bubbles. Following the sparks, occasional larger stone fragments were observed, potentially resulting from microexplosions in the stone material or shockwaves due to laser-induced cavitation bubble collapse. A more detailed investigation is warranted to ascertain the underlying causes.

This study has limitations primarily due to its reliance on in-vitro experiments. Moreover, the impact of different stone compositions (other than COM), irrigation flow rate, and irrigation fluid temperatures has not been evaluated. While our findings support the effectiveness of TFL for stone dusting, the ablation capability of TFL for certain compositions, such as calcium phosphate (CaP) stones, remains a subject of debate [15]. Additionally, TFL has a higher propensity for stone carbonization or charring with relatively soft and porous CaP stones, while producing sparks when treating hard and dense COM stones, compared to Ho: YAG lasers. These factors can potentially compromise the treatment efficiency (i.e., stone ablation speed), prolong procedure time, impact thermal safety, and potentially limit effectiveness during LL [15]. Future research in animal models is warranted to simulate the operating room environment. Quantifying the thermal effects on impacted stones in the ureter may also provide better quantification and evaluation of various effects to optimize the treatment outcomes.

Conclusions

Our study provides important insights into the optimal settings for TFL lithotripsy in the treatment of urolithiasis. The results demonstrate that the high E_P/low F settings at 0.8 J/12 Hz yield a two-fold increase in treatment efficiency, lesser residual fragments (>0.25 mm), a significant reduction in energy expenditure, and improved ablation outcomes for both BegoStone and COM stones compared to the low E_P /high F settings (0.2 J/50 Hz or 0.2 J/100 Hz) commonly used in current clinical practice. Importantly, the thermal dose remains below the threshold for tissue injury at the 0.8 J/12 Hz settings, ensuring patient safety, as compared to higher power (> 10 W) settings. Our findings challenge the existing clinical presets and emphasize the need to explore novel parameter regimes to enhance the treatment efficiency of TFL in kidney stone interventions.

Nomenclature and abbreviations

Nomenclature

CEM43°C

Cumulative equivalent minutes at 43 °C

E_P

Pulse energy in Joule (J)

F

Frequency in Hertz (Hz)

Laser energy utilization efficiency

Pulse energy in Joule (J) required to ablate a unit stone mass (in mg)

n

sample size

p

p-value for the Student’s t-test

R

Empirical constant

SD

Standoff Distance (mm)

$\tau$

Pulse duration ($\mu s)$

t

Time (seconds)

T

Temperature in °C

T1 -T6

Temperature values from the thermocouples at position 1 – 6

Tm

Melting temperature (°C)

TScope

Temperature value from the thermocouple placed at 5 mm from scope tip (°C)

Treatment efficiency

Amount of stone mass (in mg) ablated in unit time (in seconds)

Abbreviation

CaP

Calcium phosphate

COM

Calcium oxalate monohydrate

CT

computed tomography

Ho

Holmium

LL

Laser lithotripsy

NA

Numerical aperture

TFL

Thulium Fiber Laser

URS

Ureteroscopy

YAG

Yttrium Aluminum Garnet