## 1 Introduction  
In biology and medicine, many essential processes unfold at the nanoscale. Visualizing cellular structures, organelles, and biomolecules in three dimensions allows researchers to understand the complexities of biological systems, including how cells function, communicate, and respond to stimuli. This is vital for advancing our knowledge of health and disease. It is also critical for advancements in energy storage, catalysis, and environmental science. To visualize large/thick biological samples (e.g., cells and tissues), various volume electron microscopy (EM) techniques have been developed [1; 2]. In Array Tomography, sections prepared by microtome, cryo-microtome, or ultramicrotome are imaged using scanning electron microscopes (SEMs) or TEMs with a resolution larger than 60 nm (i.e., the section thickness). In serial block face SEM (SBF-SEM) or Focused Ion Beam Scanning Electron Microscopy (FIB-SEM), the top surface is imaged with repeated material removal from the top surface, and the resolution is limited by the slice thickness (\(\sim\)30-100 nm). To ensure that biological samples are as close as possible to their native state, cryo-FIB-SEM has been developed [3; 4; 5; 6; 7] with a resolution as high as a few nanometers. However, depending on the imaging parameters, it takes 15-20 h to image a 10 mm thick sample with a slice thickness of 8 nm and an area of 3 \(\times\) 2 mm\({}^{2}\) (8 nm pixel size) [7]. In addition, there are charging artifacts, curtaining artifacts, and linear artifacts [3; 5]. As shown [8; 9; 10; 11], STEM has been employed to study biological samples up to 1000 nm thick, which is much thicker than that can be imaged by cryo-Electron Microscopy (cryo-EM) or cryo-Electron Tomography (cryo-ET) [12; 13; 14; 15]. In STEM, the electron beam is focused on the specimen plane, and there is no image-magnifying lens behind it. The image is formed by mapping detector counts point-by-point to scan positions. The bright-field (BF), annular dark-field (ADF), and high-angle annular DF (HAADF) images are formed by collecting electrons within small (e.g., \(<\)10 mrad), medium (e.g., 10-50 mrad), and high (e.g., \(>\)50 mrad) angles, respectively [16; 17; 18]. For cryo-samples, objects with higher concentrations of heavy atoms will be preferentially detected by ADF imaging, forming the so-called \"Z-contrast\" (Z is the atomic number). The mass density variations in different parts of the sample are detected by BF imaging. As the allowable sample thickness depends on the electron energy and image formation mechanism, a mega-electron-volt Scanning Transmission Electron microscope (MeV-STEM) has been proposed [19]. The high penetration of inelastic scattering signals of MeV electrons could make the MeV-STEM an appropriate microscope for imaging biological samples as thick as 10 \(\upmu\)m or more with nanoscale resolution. The best resolution is inversely related to the sample thickness and changes from 6 nm to 24 nm when the sample thickness increases from 1 \(\upmu\)m to 10 \(\upmu\)m. As discussed, the resolution is mainly limited by beam broadening and low-dose limit on resolution. The broadening of the probe due to electron scattering can be estimated based on a wave optical multislice algorithm [20; 21]. The plural elastic scattering of electrons at 200 keV in vacuum and amorphous ice has been estimated by [PERSON] et al. [10]. When multiple scattering is included, the broadening of the probe is expected to be worse and needs further investigation. The Monte Carlo (MC) method is a statistical random sampling technique for solving complex multi-dimensional integral equations that are difficult to solve analytically. The general method was developed by [PERSON] and [PERSON] in 1949 [22]. It is commonly used to estimate the probability of different outcomes in a process [23; 24; 25].