Lasers in Surgery and Medicine 12:631-638 (1992)

Centering Balloon to Improve Esophageal-PhotodynamicTherapy Masoud Panjehpour, PhD, Bergein F. Overholt, MD, Robert C. DeNovo, DVM, Rick E. Sneed, BS, and Mark G. Petersen, DVM Laser/Hyperthermia Department, Thompson Cancer Survival Center, Knoxville Tennessee 37916 ( M R , B.F.O., R.E.S.), and Department of Urban Practice, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee 37901 (M.I?, B.F.O., R.C.D., M.G.P.)

A cylindrical balloon was developed to improve delivery of circumferential light for photodynamic therapy (PDT) of esophageal carcinoma. The balloon consisted of a 36-mm-long clear cylindrical membrane and a central tube to hold a cylindrical diffuser in the center of the lumen. Three isotropic probes were placed on the outside of the balloon to allow measurement of delivered light dose to the esophageal mucosa. The balloon was tested in the normal esophagus of 8 dogs that were injected with 4.0 mg/kg of PHOTOFRINR.Endoscopy was performed 48 hours following the injection, and under endoscopic observation the balloon assembly was passed, fixed in place, and inflated. A 1-cm cylindrical diffuser was passed into the central tube and 150,300, and 600 Joules/cm of 630 nm laser light was delivered at 25 cm, 15 cm, and 5 cm proximal to the gastroesophageal junction. One control dog was illuminated using the cylindrical diffuser alone at doses of 300 and 600 Joules/cm of diffuser. Complete circumferential tissue response was obtained when the balloon was used. Relatively uniform light intensities were measured around the lumen. In contrast, noncircumferential and unpredictable PDT responses were generated when the cylindrical diffuser was used without the balloon. o 1992 Wiley-Liss, Inc. Key words: cancer, photodynamic therapy, esophagus, balloon, dosimetry

INTRODUCTION

Photodynamic therapy (PDT) involves treatment of malignant tissue employing the interaction of a photosensitizer with light of appropriate wavelength in the presence of molecular oxygen. Photodynamic therapy is undergoing clinical trials for treatment of esophageal carcinoma utilizing PHOTOFRINR, porfimer sodium (previously described as dihematoporphyrin ether, DHE) and 630 nm light [1,2]. The protocol consists of an IV injection of 2.0 mg/kg of PHOTOFRINR, followed by laser light illumination 40-50 hours later. The typical light delivery technique for esophageal cancer consists of passing a cylindrical diffuser through the biopsy channel of an endoscope. The diffuser is positioned to illuminate the esophageal tumor superficially or interstitially [21. The dose of light delivered is 300 Joules per centimeter 0 1992 Wiley-Liss, Inc.

length of diffuser at a power density of 400 mW per centimeter. When planning photodynamic therapy of esophageal tumors, it is assumed that the esophagus is a hollow tubular organ and that the cylindrical diffuser is placed in the center of the lumen. In reality, proper placement and maintenance of a cylindrical diffuser in the center of the esophageal lumen are difficult. Due to endoscopic design, the diffuser exits the biopsy channel of the endoscope eccentrically resulting in deposition of more light t o one side of the esophagus. In addition, respiratory movement and esophageal moAccepted for publication August 13, 1992. Address reprint requests to Masoud Panjehpour, LaseriHyperthermia Department, Thompson Cancer Survival Center, 1915 White Avenue, Knoxville, TN 37916.

632

Panjehpour et al.

tility prevent uniform and consistent illumination of an esophageal lesion. Currently, theoretical estimation of light dose t o the esophageal wall is calculated under ideal geometrical assumptions [3,41.However, the delivered light dose to the mucosa is strongly affected by position of the fiber within the lumen. Nonuniform light dose deposition is predictable if the mucosal folds are not eliminated and the fiber is not properly positioned during the illumination. In actuality, true delivered light dose to the tumor and esophageal lumen is unknown. In this work we describe a cylindrical balloon that improves circumferential light delivery to the esophagus. It also allows measurement of delivered light dose to the esophageal mucosa using isotropic probes. MATERIALS AND METHODS Animal Model

The canine esophagus was used as a model for in vivo testing of the centering balloon. The use of animals for the study was approved by the Animal Care and Concern Committee of the College of Veterinary Medicine, University of Tennessee. All dogs weighed -20 kg. The dogs were sedated and an intravenous catheter was placed. PHOTOFRINR(Quadra Logic Technologies, Vancouver, B.C., Canada) was reconstituted with 5% dextrose to a final concentration of 2.5 mg/ml; 4.0 mgikg of PHOTOFRINR was injected intravenously. The dogs were kept indoors for the duration of the study. Centering Balloon

The balloon is comprised of two major parts: (1) a semiflexible tube consisting of two small concentric vinyl tubes, and (2) an inflatable cylindrical balloon attached to the distal end of the tube. The inner tube, used to introduce the cylindrical diffuser into the balloon, was optically clear, -78 cm in length, had an inside diameter of 1.05 mm and outside diameter of 1.47 mm. A removable stylet was placed inside the inner tube t o increase the mechanical strength during passage into the esophagus. The distal end of the inner tube was sealed t o protect the fiber. The inner tube allowed use of commercially available cylindrical diffusers for photodynamic therapy. The outer tube was used to deliver air for inflation and deflation of the balloon. It had an outside diameter of 2.82 mm and extended into the proximal end of the balloon. A one-way valve

was used at the proximal end of this tube to maintain air pressure inside the balloon. The overall length of the cylindrical balloon was 63 mm with an outside diameter of 24 mm when inflated with 25 cc of air. The balloon was tapered at both ends providing an effective cylindrical length of 36 mm. The balloon was constructed from an optically clear polyurethane membrane with thickness of -0.11 mm. Figure 1 is a schematic of the balloon with a cylindrical diffuser inside the inner tube. Isotropic probes are shown on the cross sectional view of the balloon. Figure 2 is a photograph of the balloon assembly with a fiber inserted into the balloon. This balloon was supplied by Datascope Corp. (Oakland, NJ). Light Delivery System

An argon-pumped dye-laser, Model 2016/ 375B (Spectra-Physics, Mountain View, CAI, tuned at 630 nm was used as the light source. The wavelength was verified using an optical multichannel analyzer system, OMA I11 (EG&G Princeton Applied Research, Princeton, NJ). The light was focused into a 200-pm extension fiber, Model 5220 (PDT Systems, Buellton, CA). A 400-pm 1.0 cm cylindrical diffuser, Model 4410 (PDT Systems, Buellton, CA), was attached to the extension fiber. The power from the cylindrical diffuser was measured using an integrating sphere power meter, Model 2010 (PDT Systems, Buellton, CAI. The power was adjusted to 400 mw. The power meter was calibrated at 630 nm. Mucosal Light Measurement

Three isotropic probes, Model 2818 (PDT Systems, Buellton, CAI, were attached to the outside of the balloon. The diameter of the spherical tip of these probes was -1.8 mm. The probes were fixed around the balloon at 120"from each other. The tip of the isotropic probes were in the same plane as the center of the 1.0 cm cylindrical diffuser inside the inner tube. The collected light from the probes was measured using a single channel in vivo light dosimeter, Model 2710 (PDT Systems, Buellton, CA), calibrated at 630 nm. The dosimeter provided the space irradiance in milliwatts per square centimeter. The collected light was measured from each of the three probes sequentially, and the readings were corrected for variation in probe response. The isotropy of the probes were verified by the manufacturer prior t o shipment. Figure 3 shows the delivery balloon with the three isotropic probes attached to the

633

Improving Esophageal Photodynamic Therapy

I

EXTERNAL TUBE FOR INFLATION & DEFLATION

I

v

C

-

~

1

FIBER INNER TUBE R

DIFFUSER ISOTROPIC PROBES

/ BALLOON MEMBRANE

CROSS SECTIONAL VIEW

Fig. 1. Schematic of the cylindrical balloon for esophageal photodynamic therapy. The isotropic probes are shown on the cross sectional view of the balloon.

Fig. 2. Photograph of the balloon assembly used for esophageal illumination during photodynamic therapy: (a)balloon, (b)air delivery tube, ( c )one-way valve, (d) optical fiber.

wall. The cylindrical diffuser can be seen inside the central tube.

Fig. 3. The balloon with three isotropic probes attached to the wall for measurement of the space irradiance on the esophageal mucosa: (a)balloon, (b)inner tube, ( c ) isotropic probe, (d) cylindrical diffuser.

tubated. Anesthesia was maintained with 2% inhalation of isoflurane. Endoscopy was performed Photodynamic Therapy Treatment t o determine the locations of the gastroesophAt 40-50 hours after injection of the photo- ageal (GE) junction and treatment areas relative sensitizer, the dogs were preanesthetized and in- t o the GE junction. The deflated balloon was

634

Panjehpour et al.

passed to a predetermined measurement, inflated, and fixed in position. The stylet was removed from the inner tube and the cylindrical diffuser was inserted. The insertion length of f i ber was premeasured so that the 1.0-cm cylindrical diffuser was positioned in the center of the effective length of the cylindrical balloon. Following verification of the treatment site, the endoscope was removed. Three treatments were delivered to each dog esophagus. The first treatment was delivered 5 cm proximal to the GE junction. The light dose was 600 Jouleskm of diffuser. The second treatment was 15 cm proximal t o the GE junction at light dose of 300 Joulesicm. The third treatment was delivered 25 cm proximal to the GE junction at a dose of 150 Joules/cm. In one dog, laser light was delivered through the endoscope in the standard manner used in human treatments. This dog was used as a control t o the balloon group. The photosensitizer dose in this dog was 2.0 mg/kg. The cylindrical diffuser was passed through the biopsy channel of the endoscope and the treatment area was selected. Two treatments were delivered at 5 cm and 15 cm from the GE junction. The dose of light was 600 Joules/ cm and 300 Jouleskm, respectively. Temperature Rise in the Lumen

To assure that the observed response was due to photodynamic therapy alone and no hyperthermic temperatures were present, a separate study was performed in two dogs. A thoracotomy was performed. The esophagus was exposed and a microthermocouple was placed in the muscular layer of the esophagus. The balloon was passed, inflated, and 300 Jouleskm (400 mW/cm) of light was delivered from the fiber. The thermocouple tip was in the center of the illuminated area. The temperature was recorded every 30 seconds using a data acquisition system (Dianachart, Rockaway, NJ). Response Evaluation

Two days after light illumination, the dogs were anesthetized and endoscoped for evaluation of the illuminated sites. The animals were then euthanized and necropsy performed. The esophagus was removed and the esophageal mucosa was inspected for tissue damage at different treatment sites. RESULTS

Studies were performed in the esophagus of 8 dogs t o investigate whether use of a centering bal-

loon would improve circumferential illumination of esophageal mucosa for photodynamic therapy. Endoscopic examination of the lesions indicated that complete circumferential damage was generated when the balloon was used at both 300 and 600 Jouleskm of light delivered from the cylindrical diffuser. Tissue damage in the normal esophagus was minimal at the dose of 150 Joules/cm of light. At necropsy, it was observed that narrow wedges of esophageal mucosa were occasionally undamaged. These sections comprised only a small fraction of the entire mucosal circumference (less than 7%). Endoscopic observation in these dogs indicated that the 24-mm balloon was probably too small to completely flatten the surface of the esophagus. Figure 4 is a photograph of the lesions generated with 300 and 600 Joules/cm of light in the esophagus of one dog. The length of the lesion produced from 300 Joulesicm of diffuser was -4.0 cm. The total length of lesion produced from 600 Jouleskm of diffuser was 11.3 cm; maximum tissue effect was -6 cm long. In this case, long exposure time allowed sufficient light energy t o reach the peripheral areas creating longer lesions. Histological examination of all lesions was performed with the results being presented in another work [51. In contrast to the circumferential injury seen with the balloon, small and separate islands of tissue damage were produced in the esophageal mucosa when the cylindrical diffuser was used alone without the centering balloon. The damage consisted of less than 68% of the total mucosal circumference. The length of the lesions were -2.8 cm. It appeared that the cylindrical diffuser was positioned between folds of the collapsed esophageal wall creating a “hill-andvalley” shadowing effect. This resulted in lesions where the fiber was in contact with the tissue and negligible response in other areas. Figure 5 is a photograph of lesions produced with 600 and 300 Jouleskm of light using the cylindrical diffuser alone. The light dose delivered t o the esophageal mucosa was determined by placing three isotropic probes on the balloon wall. When the balloon was inflated, the probes measured the space irradiance in mW/cmz on the esophageal mucosa. Table 1 shows the average space irradiance measured using each isotropic probe. The total light dose delivered t o the wall for each treatment group (proximal, middle, distal) is given in the last row. For example, when a light dose of 300 Joules/cm

Improving Esophageal Photodynamic Therapy

635

Fig. 4. The circumferential damage in the normal canine esophagus when the balloon was used for illumination: (a)cranial: 300 Joules/cm, (b)caudal: 600 Jouledcm.

was delivered t o the midportion of the esophagus, the three isotropic probes indicated that 27.06, 26.26, and 23.92 Joules/cm2were delivered to the esophageal mucosa. The values are expressed in mean & one standard deviation (n = 8). Temperature was measured in the esophageal wall during a typical light delivery with the balloon t o determine if hyperthermic temperatures might be reached. Figure 6 shows the temperature change measured in the esophageal wall in one dog. The temperature rise was only in the range of 0.7-0.8"C during 12.5 minutes of illumination. It is evident that insufficient power density was delivered to the esophagus t o raise the temperature to hyperthermic ranges. DISCUSSION

Evaluation of photodynamic therapy of esophageal carcinoma has been troublesome because of difficulties in light delivery techniques and the inability t o determine proper light dosimetry. Several different techniques have been used to deliver light to esophageal cancer. Initially, esophageal tumors were illuminated using a flat-

cut fiber delivered through an endoscope biopsy channel. McCaughan et al. [2] reported on superficial and interstitial delivery of laser light using straight-tip fibers. In the case of superficial illumination, they defined the light dose in terms of Joules per square centimeter of the treated area. When the fiber was implanted into the tumor, the dose was defined as the total Joules delivered from the fiber tip. Patrice et al. 141 used straighttip fibers t o deliver laser light to tumors either superficially or intralesionally . They indicated that regardless of the illumination technique the theoretical energy density [41 was 220 Joules/cm2. Cylindrical diffusers were developed to deliver the light perpendicular to the longitudinal axis of the esophagus. McCaughan et al. [21 used cylindrical diffusers to deliver surface or interstitial illumination. In this case, the light dose was defined as the energy delivered from each centimeter of the diffuser length. Delivery of light t o the esophageal tumors is often inexact because of difficulty in placing and maintaining the light source at the target area. Cardiac movement, esophageal motility, and respiratory movements all affect the ability to main-

Panjehpour et al.

636

Fig. 5. Focal damage in the canine esophagus from illumination using a cylindrical diffuser alone passed through the endoscope: (a) cranial: 300 Jouledcm, (b) caudal: 600 Joulesicm.

TABLE 1. Summary of Light Measurements Using the Three Isotropic Probes* mW/cm2 Jicm Jicm'

Probe 1 Probe 2 36.08 2 5.15 35.02 -t_ 6.01 150 300 600 150 300 600 13.53 27.06 54.12 13.13 26.26 52.52 51.93 23.86 ~ 7 . 7 2 22.25 24.50 t9.00

Probe 3

31.90 2 4.79 150 300 600 11.96 23.92 47.84 &1.79 53.58 27.16

*First row is the mean space irradiance ( n = 8) measured on the esophageal mucosa. Second row shows different light doses delivered t o three sections of the esophagus (proximal:150 Joulesicm, middle:300 Joules/cm, distal:600 Joulesicm). Third row is the corresponding energy densities delivered to the mucosa. The power density from the cylindrical diffuser was 400 mWicm. All values are expressed in mean 2 one standard deviation.

tain a probe passed through an endoscope in the same position. Several groups have attempted to improve the light delivery systems for esophageal cancer. Thomas et al. [3] developed a balloon that assumed an elongated shape measuring 8 cm long and 1 cm in diameter. This balloon was inserted into the lumen of the esophageal cancer following dilation. The balloon was inflated with 0.5% lipid emulsion to scatter the light. With the balloon fixed in place, a quartz fiber was moved from one end of the balloon to the other end within the cancerous lesion. The delivered dose of light t o the tumor was calculated assuming that the tumor

was a cylinder with a diameter of 1 cm. Their doses of light ranged from 60 to 337 Joules/cm2. Wagnieres et al. [61 developed a light distributor for PDT in the esophagus that consisted of cylindrical bulb made from plexiglass. The diameter of the bulb was designed to slightly stretch the cross section of the esophagus wall to smooth the surface. The outside diameter of different bulbs ranged from 15 to 20 mm. Laser light was delivered to a teflon diffusing tube via a 2 0 0 - ~ mmultimode optical fiber. The teflon diffusing tube was filled with transparent silicon elastomer doped with different concentrations of small TiO, parti-

"'I

Improving Esophageal Photodynamic Therapy

36.5

LASER OFF

I

I

I

637

cident light significantly. In the study reported here, isotropic probes were attached to the outside of the balloon wall. In these probes, only 1%of the total 457 steradian is shielded at the fiber connection t o the bulb [8,91. When the balloon was inflated, the isotropic probes were positioned between the balloon and the esophagus and were in contact with the esophageal wall. In this manner the exact amount of energy delivered t o the mucosa was measured. The amount of energy density deposited on the esophageal wall is also strongly affected by the diameter of the balloon. Larger balloon diameters would increase the distance between the light source and the esophageal wall resulting in reduction of the intensity (space irradiance). This in turn would result in reduction of total light dose to the tumor. Because of varying balloon sizes and luminal diameters, it is necessary t o measure the delivered light dose to the wall with isotropic probes. Using isotropic probes and a balloon, new treatment protocols could easily be developed that would specify the PDT light dose in terms of delivered energy density to the surface of the tumor (in Joules/cm2) instead of the energy delivered from the light source (in Joules or Joules/cm of diffuser). The photodynamic therapy response in tissue is strongly affected by tissue photosensitizer concentration and the delivered light energy. In our study, we initially used 2.0 mg/kg of PHOTOFRINRand delivered 150,300, and 600 Joules/ cm of light to the normal canine esophagus using the balloon. No significant PDT damage was detected in any of the dogs treated in this group [5]. In contrast, when the cylindrical diffuser was used without the balloon, appreciable focal tissue damage was observed at both 300 and 600 Joules/ cm of diffuser. We believe that using the balloon reduced the intensity of incident light on the mucosa significantly. This resulted in insufficient energy density delivered t o create injury t o normal tissue. However, when the fiber was used alone t o deliver the light, close proximity of the diffuser t o the tissue produced sufficient energy density to create islands of focal tissue damage (noncircumferential damage, see Fig. 5 ) . In this study we chose t o increase the photosensitizer dose to 4.0 mg/kg to assure mucosal damage for evaluation of the balloon performance. The light emitted from a cylindrical diffuser travels in radial and axial directions. The axial component radiates beyond the ends of the cylindrical diffuser, resulting in a cylindrical illumi-

34, 34 0

U S E R2ON

4

6

8

10

12

14

16

18

20

TIME (MINUTES)

Fig. 6. Temperature recorded in the canine esophageal wall during a typical illumination using the balloon. A nonsignificant temperature rise was induced during the 12.5 minutes of illumination.

cles t o scatter the light entering the tube. The tube acted as a cylindrical diffuser placed in the center of the plexiglass bulb. A photodiode was incorporated in the assembly for in situ control of the light dose. Allardice et al. [71 reported on a light delivery system for PDT treatment of obstructing gastrointestinal cancer. Their system consisted of a transparent olive-dilatorlike structure with a 360" window for endoluminal illumination of esophagal cancer. They used different probes with diameters ranging from 10 to 15 mm. Both ends of the window were encased with steel caps t o avoid light delivery to the normal tissue outside the window. Once the delivery system was positioned within the stricture, an optical fiber was introduced into the central channel of the window. The fiber was modified with a circumferential diffuser attached to the distal end. The light delivery was achieved by moving the fiber in small steps while holding the delivery system in place. They indicated that 350 mW/cm2 of light intensity was delivered to the tissue with 1.1watts of power for a 1.0 cm diameter window. Whereas the exact amount of energy delivered from different fibers is easily quantified, the actual energy density delivered t o the esophageal tissue is usually estimated. Estimation of the absorbed energy is based on certain geometrical assumptions that might not be valid in all cases due to irregular shape of treatment volume. In addition, multiple reflections and scattering of red light within the lumen may alter the effective in-

638

Panjehpour et al.

nation pattern with a length longer than the length of the cylindrical diffuser. Increasing the distance between the diffuser and the esophageal mucosa by the balloon would intensify this effect, resulting in illumination lengths exceeding the diffuser length. This was clearly evident in our study. Use of the diffuser alone created a focal 2.8 cm lesion, whereas a 4.0cm lesion (circumferential) was created when the balloon was utilized. The length of the lesion was increased significantly when the illumination time was increased to achieve 600 Joules/cm of diffuser. In addition, the illumination length may also be dependent upon the reflectivity of the mucosal surface, which is affected by the extent of the disease. This problem can be solved by using a 360" window on the balloon that would allow illumination of only a segment of the esophagus. Microvasculature system is believed t o be a site of PDT damage in tumors [lo]. Care must be taken not to overdistend the normal esophageal wall during balloon inflation since overdistension might compromise microcirculation in the esophageal mucosa. The diameter of our balloon was designed so the mucosal folds were eliminated essentially without overdistension and thinning of the esophagus wall. This design may not be important in the treatment of a malignant esophageal stricture but will likely be important in the treatment of small superficial cancers of the otherwise normal esophagus. Finally, photodynamic therapy has been effective in treatment of early stage esophageal cancer where the tumor is localized and noncircumferential[21. In such cases it will be desired t o illuminate only the tumor area and avoid treatment of the normal mucosa. This would be possible with a balloon of appropriate diameter with a shaded area to block illumination of normal tissue. Such balloons are currently under development at our institution. In addition, an isotropic probe in the center of the window would measure the incident light intensity on the surface of the tumor allowing for real-time calculation of required illumination time. In conclusion, a balloon was developed t o improve light delivery for esophageal PDT by eliminating the mucosal folds during illumination. Complete circumferential tissue damage was obtained. In addition, placement of isotropic probes on the balloon wall allowed measurement and

verification of relatively uniform light doses delivered to esophageal mucosa. ACKNOWLEDGMENTS

This work was supported by Thompson Foundation and Thompson Cancer Survival Center (Knoxville, TN). The experiments were performed at the Department of Urban Practice, College of Veterinary Medicine, University of Tennessee (Knoxville). PHOTOFRINR was provided by Quadra Logic Technologies (Vancouver, BC, Canada). The authors thank Datascope for providing the balloon. The authors also thank Shawna Doan for her invaluable veterinary assistance. REFERENCES 1. Marcus SL. Photodynamic therapy of human cancer: Clinical status, potential, and needs. Future Directions and Applications in Photodynamic Therapy/SPIE Institute Series Vol. IS 1990; 6:5-56. 2. McCaughan Jr JS, Nims TA, Guy JT, Hicks WJ, Williams TE, Laufman LR. Photodynamic therapy for esophageal tumors. Arch Surg 1989; 124:74-80. 3. Thomas FLJ, Abbott M, Bhathal PS, St. John DJB, Morstyn G. High-dose photoirradiation of esophageal cancer. Ann Surg 1987; 206(2):193-199. 4. Patrice T, Foultier MT, Yactayo S, Adam F, Galmiche JP, Douet MC. Endoscopic Photodynamic therapy with hematoporphyrin derivative for primary treatment of gastrointestinal neoplasms in inoperable patients. Dig Dis Sci 1990; 35(5):545-552. 5. Overholt BF, DeNovo RC, Panjehpour M, Petersen MG. A centering balloon for photodynamic therapy of esophageal cancer. Gastroenterology (submitted). 6. Wagnieres G, Monnier P, Savary M, Cornaz P, Chatelain A, van den Bergh H. Photodynamic therapy of early cancer in the upper aerodigestive tract and bronchi: Instrumentation and clinical results. Future Directions and Applications in Photodynamic Therapy/SPIE Institute Series Vol. IS 1990; 6:249-272. 7. Allardice JT, Rowland AC, Williams NS, Swain CP. A new light delivery system for the treatment of obstructing gastrointestinal cancers by photodynamic therapy. Gastrointest Endosc 1989; 35(6):548-551. 8. Dunn JB, Cusimano P, Doiron DR. In-vivo photodynamic therapy dosimeter. Proceedings of Photodynamic Therapy: Mechanisms I1 1990; 1203:32-41. 9. Marijnissen JPA, Versteeg AAC, Star WM. In vivo light dosimetry for interstitial photodynamic therapy: Results of clinical importance. SPIE 1989; 1065:109-114. 10. Wieman TJ, Mang TS, Fingar VH, Hill TG, Reed MWR, Corey TS, Nguyen VQ, Render ER. Effects of photodynamic therapy on blood flow in normal and tumor vessels. Surgery 1988; 104(3):512-517.

Centering balloon to improve esophageal photodynamic therapy.

A cylindrical balloon was developed to improve delivery of circumferential light for photodynamic therapy (PDT) of esophageal carcinoma. The balloon c...
808KB Sizes 0 Downloads 0 Views