## 2 Materials and Methods
### Materials and Conditions for the Simulation and Experiment  
In simulation, the used Lena image was of size 512 \(\times\) 512 pixels and three-dimensional (3D) (i.e., width, height, and depth (3-color channel)). A simulation study was performed using Lena images to evaluate prior possibilities before applying the proposed algorithm to real light microscopy images. Here, the image was properly selected to perform the simulation because of its well-matched detail, shadow, and texture, which is good for handling the proposed algorithm. Figure 4 shows the blurred PSF (\(\sigma_{PSF}\) = 1, arbitrarily unit) plot and Gaussian noise image (\(mean\) = 0 and \(variance\) = 0.01) to generate the degraded image, as shown in Equation (1). Noise generation was performed using _innoise_ function (MATLABTM, R2021a, Mathworks, Natick, MA, USA). These values are different from the image degradation that occurs when acquiring light microscopy images in our experiments. However, they are arbitrarily assigned to perform a quantitative performance evaluation of the proposed algorithm and are sufficient for the original purpose of performing the simulation.  
In experiment, microscopy images were obtained using a Leica DM500 microscope and Leica ICC50 E camera (Leica Microsystem, Wetzlar, Germany, readout noise (\(\sigma\)) \(<\) 6 least-significant bit, typical), and Leica LAS EZ 3.0 software (Leica Microsystem, Wetzlar, Germany). In this work, we aim to derive optimal PSF and to restore the intrinsic resolution of optical microscopy system. ICR male mice (Orientbio, Seongnam, Republic of Korea) were used to obtain the light microscopic images. The mandibles were dissected from the mice and immediately fixed in 4% paraformaldehyde (PFA) at 4 \({}^{\circ}\)C for 24 h. For decalcification, the samples were treated with 10% ethylenediaminetetraacetic acid (EDTA) for four weeks. The specimens were dehydrated and embedded in paraffin. They were cut to a thickness of 7-\(\mu\)m and stained with hematoxylin and eosin (H&E) routinely used for histological examination. Histological images including the bone, periodontal ligament (PDL), and tooth of mandible were taken under the light microscope. Exposure times ranged from 2 ms to 600 s, and implemented the gain, offset, and shading correction. Numerical aperture (NA) value is 0.280, field of depth at dry objective is about 8 \(\mu\)m, 400\(\times\) magnification is used in this study.  
Based on the above descriptions, we implemented the proposed algorithm using computing environment: CPU: Intel, Santa Clara, CA, USA, Xeon Platinum 8168 @ 2.70 GHz; RAM: Samsung, Suwon, Republic of Korea, 8 G \(\times\) 4 DDR4 21,300; GPU: NVIDIA, Santa Clara, CA, USA, GTX 1080 11 GB. The acquired microscopy image is in tiff format and composed of 3-channel data, which were derived by applying the proposed algorithm to the obtained images in the wavelet domain. The processing time of proposed algorithm in 512 \(\times\) 512 pixels image is approximately less than 2 s with the GPU parallel processing, which confirms the utility for practical applications.  
Figure 4: (**a**) 3D PSF plot (\(\sigma_{PSF}\) = 1) and (**b**) 2D image of Gaussian noise (mean = 0 and \(\sigma_{N}\) = 0.01).