**1. Introduction**

Topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) and its variants as the methyl-aminolevulinate (MAL) is a well-established technique that requires a light source appropriate to a specific application, such as cancer types and precancerous lesions [1, 2]. ALA and its variants are the main precursors of protoporphyrin IX (PpIX), which is an endogenous photosensitizer (PS) and it is part of the heme biosynthesis pathway. PpIX selectively sensitizes the diseased cells, and when it is excited by light of a certain wavelength, interact with molecular oxygen producing reactive cytotoxic species, causing cells death by necrosis, apoptosis or autophagy. However, for PDT to work is required, a PS, the wavelength to excite the PS, and the molecular oxygen present in the tissue [3].

Lasers and light-emitting diodes (LEDs) are suitable light sources for PDT applications. But fiber-optic-lasers are more appropriate for light endoscopes device, or even for intraoperative cavities illumination. In general, illumination devices have light emitters of fixed geometry. An exception is the recently developed fabric-like material made with single-mode optical fibers adjustable to a specific application or anatomic site [4–6].

Several authors have reported PDT applications in dermatology for not only non-melanoma skin cancer but esthetic treatments [7–10]. Therefore, laser devices with optical fibers are not convenient, since large areas and anatomic sites must be considered.

On the other hand, Light Emitting Diodes (LEDs) are an alternative illumination system and can deliver the necessary intensities for PDT performance at lower costs. LED devices have already been used in PDT for the treatment of skin cancer and esthetic procedures [11–16], however, its field of illumination is limited and it is not anatomically adjustable to the body, which hampers the treatment of areas not reached by the light. Moreover, it is not effective for the treatment of large lesions located in the head, neck, legs, and arms, due to its non-conformability, which causes the illumination not to be homogenous. An example is the treatment of actinic keratosis (AK), which are lesions more likely to occur on the face and scalp due to high exposure to the sun [6–10].

The treatment of AK with photodynamic therapy requires illumination of the entire region at the same intensity. In this case, the anatomical device enables the use of the PDT procedure and optimizes the application time.

The topical application of the ALA prodrug and its derivatives in PDT can be used by several light sources, so long as the photosensitive agents are activated by the wavelengths. Because the PpIX accumulated by the application of the prodrug has absorption peaks in the Soret band and four minor peaks in the Q band, 510 nm, 545 nm, 580 nm, and 630 nm. Thus, blue light-emitting at 450 nm and red lightemitting at 630 nm from LED devices can be applied for the activation of PpIX. However, blue light penetrates superficial layers of the skin and red-light deeper layers of the skin [17–20].

Our main concern was to produce a flexible LED illumination system of highpower that operates at 450 ± 10 nm and 630 ± 10 nm wavelengths; therefore, the device was tested by engineers and in clinical applications (AKs treatment and esthetic dysfunctions) [20, 21].

#### **2. Illumination systems: small, fixed and adjustable array**

**Figure 1a** shows LINCE® (MMOptics, São Carlos, SP, Brazil) device, it is treatment system and comprised of a circular probe (on the left) with approximately 9.0 cm2 area that emits at 630 nm ± 10; on the right, it is a diagnostic system, which emits at 405 ± 10 nm and collects the image of the protoporphyrin IX formation induced by a topical application of a precursor on the skin. **Figure 1b** displays a square illumination of LINCE® accessory in a 61 cm<sup>2</sup> area, with LEDs (lightemitting diodes) emitting at 630 ± 10 nm.

The system is recommended for small lesions, such as superficial or nodular Basal Cell Carcinoma (BCC). It was developed in the Brazilian Skin Cancer PDT program, currently, already it is used in the clinics. [1, 4, 13–15].

The device was designed for improving the large area attachment of LINCE® accessory and providing an extra accessory that can multiply the possibilities of the Clinical PDT treatment. It was developed in cooperation with MMOptics industry (São Carlos, SP, Brazil) and Technological Support Laboratory (São Carlos Institute of Physics, University of São Paulo, São Carlos, SP, Brazil) and assembled by rectangular modules (up to 10, in principle).

However, a version with 5 modules composing a 192 cm2 area of illumination (**Figure 2a**) was employed in this study. It consists of five LEDs (Luxeon Rebel, Lumileds Company) boards, thus totaling 30 LEDs emitting at 630 ± 10 nm, and 25 *Anatomically Adjustable Device for Large-Area Photodynamic Therapy DOI: http://dx.doi.org/10.5772/intechopen.93917*

#### **Figure 1.**

*(a) LINCE® equipment (MMOptics – Brazil): left - treatment system emitting at 630 nm; right - diagnostic system emitting at 405 ± 10 nm. (b) Square illumination of the LINCE® accessory emitting at 630 ± 10 nm.*

#### **Figure 2.**

*Anatomically adjustable device. (a) Front of the equipment, where the LEDs are coupled and protected by plastic covers. (b) Side of the device, with an acrylic tube that facilitates its handling. (c) Adaptation of its curvature to the body by the acrylic tube. (d) Electronic box with the sequence of the drive buttons.*

LEDs emitting at 450 ± 10 nm. A flexible tube was added for adapting the equipment to regions of the body (**Figure 2b**), and a handle facilitated its use in areas of curvature (**Figure 2c**) and avoided the bending of the plates with LEDs. Power sources of 16 V for emission at 450 ± 10 nm, and 5 V for emission at 630 ± 10 nm, both with 3 A electric current, are connected to the device. Below is the description of the power buttons (**Figure 2d**):


4.Button that turns on the equipment according to the wavelength selected (1).

5.Button that disables the equipment if pressed for a few seconds.

**Figure 3** shows the way the equipment can be used in different parts of the body, according to an adequate anatomic configuration.

**Figure 4** shows LINCE® (MMOptics, São Carlos, SP, Brazil) lighting system and its accessory (the 61 cm2 fixed array) for the treatment of large areas. LINCE® is not adequate for treatments that require illumination of a larger area, since it does not have good applicability - it must be pushed away, which reduces the intensity and increases the application time. LINCE® accessory (the 61 cm<sup>2</sup> fixed array) has a larger area; however, it is fixed and does not fit the body anatomy. The delivered dose decreases when it moved away from the patient's skin, and a longer time is

#### **Figure 3.**

*Possible configurations of the device for different regions of the body. (a) Neck; (b) shin; (c) back; (d) quadriceps and (e) head.*

#### **Figure 4.**

*Images of a treatment performed on the face. Devices emit at 630 nm. (a) LINCE® (MMOptics, São Carlos, SP, Brazil) - illumination system for treatment. (b) LINCE® accessory.*

*Anatomically Adjustable Device for Large-Area Photodynamic Therapy DOI: http://dx.doi.org/10.5772/intechopen.93917*

necessary for the achievement of the desired effect. In addition, the irradiance delivered on the target tissue is not homogeneous.

**Figure 5** shows the PDT treatment for AK and acne vulgaris by the anatomical device.

AKs lesions often appear scattered in a specific region of the body most exposed to the sun. The device optimizes the PDT treatment so that it covers extensive regions and delivers the necessary intensity. **Figure 5a** shows the device used for the treatment of AKs at the back of the hand. The device enabled the treatment of both hands concomitantly. **Figure 5b** displays the device being used in patients with actinic keratosis on top of the head. The shape of the device adjusted to the anatomy of the region promotes uniform illumination and covers the entire area of lesions, thus reducing the number of exposures needed to treat larger areas effectively.

**Figure 5c** and **d** show the device being used for the treatment of acne vulgaris in the face. It was leaned against the treated area so that the desired intensity and fluency rate could be delivered. The equipment was moved a little away from the patient to allow a clearer photograph and the area treated. A flat device would not treat the surface so closely and uniformly.

### **2.1 Optical characteristics - adjustable array**

The light distribution was measured using the laser power meter (LabMax-TOP, Coherent Inc., Santa Clara, USA). It has a 0.5 cm2 circular area sensor and the wavelength was configured for the collection of the intensity measured. The light distribution was measured 5 cm away from the equipment, and the power meter

**Figure 5.**

*(a) AK treatment with the anatomical device at the back of the hand. Both hands can be treated concomitantly. (b) AK treatment with the anatomical device in the head region, covering its whole region. (c) and (d) PDT procedure for acne vulgaris on the face.*

sensor was scanned throughout the device area. The distance from each point collected was the diameter of the power meter detector.

**Figure 6** shows the measurement of intensity (collected point to point) of the light emission of the anatomical device.

The device remained on for 20 minutes to perform the warm-up test, and it did not heat up, which has proven the light-emitting surface causes no thermal damage to the skin.

Planar irradiance distribution was mapped out at a range of distances from the light source. Measurements were collected from the distance zero until 5 cm of the laser power meter, varying each 1 cm (**Figure 7**). The covered area of the measurements corresponds to 192 cm2 (13 × 15 cm). The intensity fluctuates with a small decay at the boundary for both wavelengths. We calculated the average intensity, considering a continuous emitting surface (**Figure 8**). The intensity at any z-axis from the emitting surface can be evaluated through the integration of all elementary emitters.

To calculate the intensity at a certain position (x, y, z) above the surface, we can proceed with the sum of the contributions of all the emitters distributed on the surface. Imagine that in each position determined by the coordinates (x', y') there is an emitting element. The contribution of all of them to the intensity at the point

#### **Figure 6.**

*Intensity measurements were collected from point to point in the anatomical device area. (a) Intensity emitting at 630 ± 10 nm and (b) intensity emitting at 450 ± 10 nm.*

*Intensity versus distance. The intensity was measured by LabMax-TOP laser power meter (Coherent Inc., Santa Clara, USA). Measurements were collected every 1 cm from the device up to 5 cm and scanned throughout the device area.*

#### **Figure 8.**

*Average intensity calculated by the integral of the elementary emitters at any point of the intensity (x*′ *,y*′ *).*

outside the surface (x, y, z) is then given by the integral of all elements, covering the entire area that contains emitters. Considering as in **Figure 8**, where we represent in a simplified way the position of the issuer and the point considered, we have the integral:

$$I(\mathbf{x}, \mathbf{y}, \mathbf{z}) = I \bullet \iint\_{all \, surface} \frac{d\mathbf{x}' d\mathbf{y}'}{\left(\mathbf{x} - \mathbf{x}'\right)^2 + \left(\mathbf{y} - \mathbf{y}'\right)^2 + \mathbf{z}^2} \tag{1}$$

If we consider a special point of interest, the central point of the distribution (x = 0 and y = 0), we have that the previous integral is reduced to:

$$I(\boldsymbol{x}) = \operatorname{Io} \coprod\_{\text{all surface}} \frac{d\boldsymbol{x}'d\boldsymbol{y}'}{\boldsymbol{x}^2 + \boldsymbol{y}^2 + \boldsymbol{z}^2} \tag{2}$$

If 0*I* is close to the emitters intensity (z → 0), the intensity at point (x, y, z) is given by (3)

$$I\left(\varkappa,\mathcal{y},\mathcal{z}\right) = I\_o \int\_{-a-b}^{+a+b} \frac{d\varkappa' d\mathcal{y}'}{\left(\varkappa - \varkappa'\right)^2 + \left(\mathcal{y} - \mathcal{y}'\right)^2 + \left(\varkappa - \varkappa'\right)^2}.$$

At the center of the illuminating area (x = y = 0), at any distance z

$$I\left(z\right) = I\_0 \int\_{-a-b}^{+a+b} \int\_{\mathbf{x}'^2} \frac{d\mathbf{x}'d\mathbf{y}'}{\mathbf{x}'^2 + \mathbf{y}'^2 + \mathbf{z}'^2} \tag{4}$$

The integral can be solved by traditional approximation and results in a center average intensity of

$$I(z) = \pi I\_0 \ln \left( \frac{4ab}{\frac{\pi}{\pi}} + z^2 \right) \tag{5}$$

The calibration of 0*I* at certain *z* provides a center intensity at a distance z from the device shown in **Figure 9**.

**Figure 9.** *Intensity decay caused by an increase in the distance from the device to the target tissue.*

*Anatomically Adjustable Device for Large-Area Photodynamic Therapy DOI: http://dx.doi.org/10.5772/intechopen.93917*

The ideal distance for the treatment is up to 1 cm because since the presence of the emitter is dominant in this distance, the intensity fluctuates. Therefore, if the expected average is considered the center intensity, the dose can be obtained from **Figure 9**, and for each 1 s illumination, the intensity (mW/cm<sup>2</sup> ) corresponds to the 10−3 J/cm2 total dose delivered. At a 1 cm distance, the total dose delivery is 1.32 J/cm<sup>2</sup> energy, while at 5 cm distance, it decays to 0.39 J/cm<sup>2</sup> .

Generally, the total dose applied in the PDT procedures ranges from 30 to 100 J/cm<sup>2</sup> , so that for device equates a 22 to 66-minute application time, respectively. This time increases if the illumination distance increases. Those times are equivalent to 450 ± 10 nm and 630 ± 10 nm emissions.
