Patent Description:
Microscopy is used in several applications and use cases to analyze samples, such as a hospital, a lab or a clinic. A large volume of slides may need to be read at a microscope facility, and the throughput of such systems can be less than ideal. Commercial microscopes, such as whole slide imaging (WSI) devices that are currently available, often comprise a single scanning microscope that relies primarily on accurate mechanical scanning and high-quality objective lenses. Recently computational microscopy has been proposed as a way of improving the resolution of optical images. With computational microscopy, a plurality of images of the sample can be obtained and processed to improve resolution and quality.

With these prior approaches to microscopy, the throughput may still be limited by the speed in which the scanning microscope can scan a single slide, and by the computational time to generate the image in at least some instances. The prior approaches may less than ideally allocate microscope and processing resources and may sample and process more sample data than would be ideal. This can result in delays, resulting in less than ideal throughput.

Some facilities such as pathology labs and hospitals may scan several microscope samples, and the throughput of the prior systems can be less than ideal. For example, some samples such as frozen samples, may need to be read quickly, while other samples may be less time sensitive. In addition, some samples may be read while a patient is in surgery to determine how to treat the patient surgically. Also, the samples obtained from tissue and other objects may contain artifacts or empty regions that are not helpful in evaluating the sample. For example, with some tissue samples such as needle biopsies and microtomes, the sample on the microscope slide can be distributed unevenly.

The prior approaches to microscopy may scan more of the sample than would be ideal. For example, regions that contain artifacts or empty space may not be helpful in evaluating the sample. Examples of artifacts include particulate matter, dust, dirt, debris, and smudges. The artifacts and empty space on the sample will generally not be helpful in analyzing the sample. The prior approaches to microscopy can scan and process these regions with artifacts and empty space with resources similar to other regions that contain useful sample material, resulting less than ideal throughput for the output images.

In light of the above, it would be desirable to have improved methods and apparatus for increasing microscope imaging throughput at facility. Ideally, such improved microscope systems would overcome at least some of the aforementioned limitations of the prior approaches.

<CIT> describes a microscope system comprising a low resolution image generation part that acquires a low resolution image by observing a specimen through a low magnification objective lens by a microscope device; an attention area setting part that extracts an expression area of the target molecule from the low resolution image on the basis of color information on the low resolution image and sets the expression area as an attention area; a focusing plane determination part that determines a focusing plane with respect to the attention area; and a high resolution image generation part that acquires a high resolution image by observing an area of the specimen corresponding to the attention area through a higher magnification objective lens than the low magnification objective lens by the microscope device on the basis of the focusing plane determined by the focusing plane determination part.

A paper by <NPL>) describes a microscopy-based scanning and analysis system.

<CIT> describes a microscope including an illumination assembly configured to illuminate the sample under two or more different illumination conditions. The microscope further includes at least one image capture device configured to capture image information associated with the sample and at least one controller. The at least one controller is programmed to receive, from the at least one image capture device, a plurality of images associated with the sample. At least a first portion of the plurality of images is associated with a first region of the sample, and a second portion of the plurality of images is associated with a second region of the sample. The at least one controller is further programmed to initiate a first computation process to generate a high resolution image of the first region by combining image information selected from the first portion of the plurality of images; receive, after initiating the first computation process and before completing the first computation process, a request associated with prioritizing a second computation process for generating a high resolution image of the second region; and initiate, after receiving the request, the second computation process to generate the high resolution image of the second region by combining image information selected from the second portion of the plurality of images.

The present invention is defined in the appended independent claim. Optional features are defined in the dependent claims.

The accompanying drawings illustrate a number of examples of the present disclosure and are a part of the specification.

Throughout the drawings, identical reference characters and descriptions indicate similar, but not necessarily identical, elements. While the examples described herein are susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and will be described in detail herein. However, the examples described herein are not intended to be limited to the particular forms disclosed. Rather, the instant disclosure covers all modifications, equivalents, and alternatives falling within the scope of the appended claims.

The presently disclosed microscope methods and apparatus disclosed herein can be used to measure many types of samples and generate computational images. The microscope can be configured to measure regions that comprise artifacts or are empty or dirty, for example. The images comprise a computational image. By selectively identifying regions of the sample that are less useful, the speed of the imaging process can be increased. The methods and apparatus disclosed herein are well suited for use with one or more components of prior systems. For example, the microscope methods and apparatus disclosed herein can be readily incorporated into prior systems, for example with a software upgrade.

The artifact as described herein such as particulate matter, e.g. dust or debris, may be located from a focal plane of the microscope or within it. The processor can be configured with instructions to determine whether specific artifacts, portions or areas of the processed images originate from locations away from the focal plane, for example by exhibiting different shifts among an image set in response to a different illumination angle of the illumination beam.

<FIG> is a diagrammatic representation of a microscope <NUM>. The term "microscope" as used herein generally refers to any device or instrument for magnifying an object which is smaller than easily observable by the naked eye, i.e., creating an image of an object for a user where the image is larger than the object. One type of microscope may be an "optical microscope" that uses light in combination with an optical system for magnifying an object. An optical microscope may be a simple microscope having one or more magnifying lens. Another type of microscope may be a "computational microscope" that comprises an image sensor and image-processing algorithms to enhance or magnify the object's size or other properties. Enhancements may include resolution enhancement, quality improvement (e.g., aberration correction, computational refocusing, contrast enhancement, distortion correction, color enhancement, registration, removing certain elements of the data, etc.). The computational microscope may be a dedicated device or created by incorporating software and/or hardware with an existing optical microscope to produce high-resolution digital images. As shown in <FIG>, microscope <NUM> comprises an image capture device <NUM>, a focus actuator <NUM>, a controller <NUM> connected to memory <NUM>, an illumination assembly <NUM>, and a user interface <NUM>. An example usage of microscope <NUM> may be capturing images of a sample <NUM> mounted on a stage <NUM> located within the field-of-view (FOV) of image capture device <NUM>, processing the captured images, and presenting on user interface <NUM> a magnified image of sample <NUM>.

Image capture device <NUM> is used to capture images of sample <NUM>. In this specification, the term "image capture device" as used herein generally refers to a device that records the optical signals entering a lens as an image or a sequence of images. The optical signals may be in the near-infrared, infrared, visible, and ultraviolet spectrums. Examples of an image capture device comprise a CCD camera, a CMOS camera, a photo sensor array, a video camera, a mobile phone equipped with a camera, a webcam, a preview camera, a microscope objective and detector, etc. Some examples of the present disclosure may comprise only a single image capture device <NUM>, while other examples may comprise two, three, or even four or more image capture devices <NUM>. In some examples, image capture device <NUM> may be configured to capture images in a defined field-of-view (FOV). Also, when microscope <NUM> comprises several image capture devices <NUM>, image capture devices <NUM> may have overlap areas in their respective FOVs. Image capture device <NUM> may have one or more image sensors (not shown in <FIG>) for capturing image data of sample <NUM>. In other examples, image capture device <NUM> may be configured to capture images at an image resolution higher than VGA, higher than <NUM> Megapixel, higher than <NUM> Megapixels, higher than <NUM> Megapixels, <NUM> Megapixels, higher than <NUM> Megapixels, higher than <NUM> Megapixels, or higher than <NUM> Megapixels. In addition, image capture device <NUM> may also be configured to have a pixel size smaller than <NUM> micrometers, smaller than <NUM> micrometers, smaller than <NUM> micrometers, smaller than <NUM> micrometers, or smaller than <NUM> micrometer.

Microscope <NUM> may comprise focus actuator <NUM>. The term "focus actuator" as used herein generally refers to any device capable of converting input signals into physical motion or changing ray convergence for adjusting the relative distance between sample <NUM> and image capture device <NUM>. Various focus actuators may be used, including, for example, linear motors, electrostrictive actuators, electrostatic motors, capacitive motors, voice coil actuators, magnetostrictive actuators, liquid lenses, etc. Focus actuator <NUM> may comprise an analog position feedback sensor and/or a digital position feedback element. Focus actuator <NUM> is configured to receive instructions from controller <NUM> in order to make light beams converge to form a clear and sharply defined image of sample <NUM>. In the example illustrated in <FIG>, focus actuator <NUM> may be configured to adjust the distance by moving image capture device <NUM>.

However, in other examples, focus actuator <NUM> may be configured to adjust the distance by moving stage <NUM>, or by moving both image capture device <NUM> and stage <NUM>. Microscope <NUM> may comprises controller <NUM> for controlling the operation of microscope <NUM> according to the disclosed examples. Controller <NUM> may comprise various types of devices for performing logic operations on one or more inputs of image data and other data according to stored or accessible software instructions providing desired functionality. For example, controller <NUM> may comprise a central processing unit (CPU), support circuits, digital signal processors, integrated circuits, cache memory, or any other types of devices for image processing and analysis such as graphic processing units (GPUs). The CPU may comprise any number of microcontrollers or microprocessors configured to process the imagery from the image sensors. For example, the CPU may comprise any type of single-or multi-core processor, mobile device microcontroller, etc. Various processors may be used, including, for example, processors available from manufacturers such as Intel", AMD®, etc. and may comprise various architectures (e.g., x86 processor, ARM®, etc.). The support circuits may be any number of circuits generally well known in the art, including cache, power supply, clock and input-output circuits. Controller <NUM> may be at a remote location, such as a computing device communicatively coupled to microscope <NUM>.

Controller <NUM> may be associated with memory <NUM> used for storing software that, when executed by controller <NUM>, controls the operation of microscope <NUM>. In addition, memory <NUM> may also store electronic data associated with operation of microscope <NUM> such as, for example, captured or generated images of sample <NUM>. In one instance, memory <NUM> may be integrated into the controller <NUM>. In another instance, memory <NUM> may be separated from the controller <NUM>.

Specifically, memory <NUM> may refer to multiple structures or computer-readable storage mediums located at controller <NUM> or at a remote location, such as a cloud server. Memory <NUM> may comprise any number of random access memories, read only memories, flash memories, disk drives, optical storage, tape storage, removable storage and other types of storage.

Microscope <NUM> comprises illumination assembly <NUM>. The term "illumination assembly" as used herein generally refers to any device or system capable of projecting light to illuminate sample <NUM>.

Illumination assembly <NUM> may comprise any number of light sources, such as light emitting diodes (LEDs), LED array, lasers, and lamps configured to emit light, such as a halogen lamp, an incandescent lamp, or a sodium lamp. In one example, illumination assembly <NUM> may comprise only a single light source. Alternatively, illumination assembly <NUM> may comprise four, sixteen, or even more than a hundred light sources organized in an array or a matrix. In some examples, illumination assembly <NUM> may use one or more light sources located at a surface parallel to illuminate sample <NUM>. In other examples, illumination assembly <NUM> may use one or more light sources located at a surface perpendicular or at an angle to sample <NUM>. Illumination assembly <NUM> may comprise other optical elements, such as lenses, mirrors, diffusers, active or passive phase elements, intensity elements, etc..

Illumination assembly <NUM> is configured to illuminate sample <NUM> in a series of different illumination conditions. In one example, illumination assembly <NUM> may comprise a plurality of light sources arranged in different illumination angles, such as a two-dimensional arrangement of light sources. In this case, the different illumination conditions comprise different illumination angles. For example, <FIG> depicts a beam <NUM> projected from a first illumination angle α1, and a beam <NUM> projected from a second illumination angle α2. In some examples, first illumination angle α1 and second illumination angle α2 may have the same value but opposite sign. In other examples, first illumination angle α1 may be separated from second illumination angle α2. However, both angles originate from points within the acceptance angle of the optics. In another example, illumination assembly <NUM> may comprise a plurality of light sources configured to emit light in different wavelengths. In this case, the different illumination conditions comprise different wavelengths. In yet another example, illumination assembly <NUM> may configured to use a number of light sources at predetermined times. In this case, the different illumination conditions comprise different illumination patterns. According to the invention defined in claim <NUM>, the plurality of illumination conditions comprises at least one of an illumination angle, an illumination wavelength, an illumination pattern, illumination intensity, or illumination position.

Microscope <NUM> may comprise, be connected with, or in communication with (e.g., over a network, via dedicated connection (e.g., HDMI, VGA, RGB, Coaxial) or wirelessly, e.g., via Bluetooth or WiFi) user interface <NUM>. The term "user interface" as used herein generally refers to any device suitable for presenting a magnified image of sample <NUM> or any device suitable for receiving inputs from one or more users of microscope <NUM>. <FIG> illustrates two examples of user interface <NUM>. The first example is a smartphone or a tablet wirelessly communicating with controller <NUM> over a Bluetooth, cellular connection or a Wi-Fi connection, directly or through a remote server. The second example is a PC display or monitor physically connected to controller <NUM>. In some examples, user interface <NUM> may comprise user output devices, including, for example, a display, tactile device, speaker, etc. In other examples, user interface <NUM> may comprise user input devices, including, for example, a touchscreen, microphone, keyboard, pointer devices, cameras, knobs, buttons, etc. With such input devices, a user may be able to provide information inputs or commands to microscope <NUM> by typing instructions or information, providing voice commands, selecting menu options on a screen using buttons, pointers, or eye-tracking capabilities, or through any other suitable techniques for communicating information to microscope <NUM>. User interface <NUM> may be connected (physically or wirelessly) with one or more processing devices, such as controller <NUM>, to provide and receive information to or from a user and process that information. In some examples, such processing devices may execute instructions for responding to keyboard entries or menu selections, recognizing and interpreting touches and/or gestures made on a touchscreen, recognizing and tracking eye movements, receiving and interpreting voice commands, etc..

Microscope <NUM> may also comprise or be connected to stage <NUM>. Stage <NUM> comprises any horizontal rigid surface where sample <NUM> may be mounted for examination. Stage <NUM> may comprise a mechanical connector for retaining a slide containing sample <NUM> in a fixed position. The mechanical connector may use one or more of the following: a mount, an attaching member, a holding arm, a clamp, a clip, an adjustable frame, a locking mechanism, a spring or any combination thereof. Stage <NUM> may comprise a translucent portion or an opening for allowing light to illuminate sample <NUM>. For example, light transmitted from illumination assembly <NUM> may pass through sample <NUM> and towards image capture device <NUM>. Stage <NUM> and/or sample <NUM> may be moved using motors or manual controls in the XY plane to enable imaging of multiple areas of the sample.

<FIG> is a diagram of an exemplary sample <NUM> comprising a plurality of areas or regions, in which some of the areas comprise valid sample portions and other areas comprise one or more of artifacts or empty space. The sample <NUM> comprises a plurality of areas that can be evaluated to determine whether the areas comprise valid sample data, artifacts or empty space. The sample <NUM> may comprise a valid portion <NUM> generally extending across a plurality of areas. The valid portion <NUM> of the sample <NUM> may comprise an edge <NUM>, which may extend through a plurality of imaged areas of the sample. The plurality of areas may comprise a first area <NUM>. The first area may comprise a valid portion of the sample and an unreliable portion of the sample comprising artifact or empty space. For example, the plurality of areas may comprise an empty area <NUM>, corresponding to voids in the valid portion. The empty area <NUM> is identified by the microscope comprising the processor as described herein, and the processor changes the imaging process in response to the identified area. The plurality of areas may comprise a third area <NUM> comprising artifacts as described herein such as particulate matter, for example. The sample <NUM> may comprise a fourth area <NUM> comprising a portion of valid sample over at least a portion of the region. Valid portion <NUM> comprises material such as biological material that is of interest and can be used to generate high resolution images. The microscope <NUM> is configured to change the imaging process for some areas of the sample and only partially process areas <NUM> and <NUM>, for example. This has the advantage of reducing processing by microscope <NUM> and expediting computational or other imaging of sample <NUM>. The regions of the sample comprising at least a portion of the valid sample, such as regions <NUM> and <NUM> are imaged with higher resolution.

The processor is configured with instructions to generate the computational image in accordance with regions corresponding to the identified areas of the sample comprising valid sample data, artifacts or empty space. The computational image may comprise a higher spatial resolving power at regions corresponding to valid portion <NUM>, and lower spatial resolving power at regions outside valid portion <NUM>. For example, regions of the computational image corresponding to region <NUM> and <NUM> may comprise lower spatial resolving power. The lower resolution image may comprise the same number of pixel density as other regions, which can be generated by empty magnification or interpolation. These approaches can provide pixel resolution enhancement without increasing spatial resolving power of the portion image, and the processor can be configured with appropriate instructions.

<FIG> is a flowchart showing an exemplary process <NUM> for accelerating digital microscopy scans using an empty and/or dirty area detection. Microscope <NUM> illuminates a sample, such as sample <NUM> of <FIG>, under observation, at step <NUM>. Image capture device <NUM> of microscope <NUM> captures an initial image set of the illuminated sample at step <NUM>. The order of steps <NUM> and <NUM> can be changed, and these steps can be performed in parallel or in a repeating fashion until the image set is captured. Also, other steps can be used, such as generating a composite image or partial computational image of the sample.

A processor of microscope <NUM>, such as controller <NUM>, tests whether an area of at least one image has artifact and/or empty space, at step <NUM>. For example, the processor may scan sample <NUM> and identify areas <NUM> and/or <NUM> as empty or having artifact, e.g., having no discernible viewing interest. Alternatively or in combination, information from a plurality of images, such as a computational image or appearance of artifacts in several images, can be used with step <NUM>. In some examples, the processor is configured with instructions to search for valid data, and determine that the area is empty or contains artifacts if the amount of valid data found in the area is under a threshold amount or does not meet a defined criterion for valid data. The processor is configured with instructions to identify areas comprising artifact or empty space, or instructions to identify valid data, and combinations thereof. The processor can be configured with instructions to separately test for each of artifacts or empty space, either separately or in combination.

The area or regions of the sample under test can be provided in step <NUM> in many ways and in some examples without steps <NUM> and <NUM>. For example, the area under test can be provided to the processor and processed to determine whether the area has valid data, artifact or empty space. Any source of image data as described herein can be used to perform the test at step <NUM>.

At step <NUM> the processor determines whether an area has artifact and/or empty space.

The test for artifact and/or empty data can be configured in many ways either alternatively or in combination. For example, the test can be performed on a composite image or a computational image or from analyzing similarities or differences between images (e. g a portion which may look like valid data in a single image or some of the images may not be present in other images and may be interpreted as an artifact). Also, the test can be performed on any one or more images of the image set, or any portion of the one or more images of the image set, or other image data for example. This test can be configured to determine when there is valid data, artifacts or empty space. Also, the testing can be configured to provide statistical data such as a probability that the area or region comprises, valid data, artifacts, or empty space, as described herein. The probability can be used to suggest that the tested area or region comprises valid data, artifacts, or empty space. Also, additional or alternative metrics to probability can be used, such as analysis of spatial frequencies, to test the area or region. In this regard, the test can determine whether the area potentially has artifact. At step <NUM>, the "yes" or "no" test can be performed based on a statistical or other analysis to alter the process as described herein.

If the area comprises artifact or empty space, the processor may direct microscope <NUM> to skip the area and/or only partially process the area to reduce computational imaging at step <NUM>. This process can be employed during the acquisition of images with the image capture device, or later during the image reconstruction process, and combinations thereof. If the area does not comprise artifact or empty space, the area can be process with high resolution at step <NUM>. Although a high resolution process is shown, other processes can be performed either alternatively or in combination. The process may improve other aspects of the image related to image quality, such as quality improvement, aberration correction, computational refocusing, contrast enhancement, distortion correction, color enhancement, registration, removing identified elements of the data. The removed identified elements of the data may comprise one or more of artifact, dust or empty space.

The processor may also flag the areas having artifact and/or empty space for subsequent imaging at step <NUM>. For example, as microscope <NUM> initiates more in-depth computational imaging of the sample, those areas of the sample that are of little or no interest may be flagged such that microscope <NUM> forgoes any additional processing of those areas.

At a step <NUM>, the imaging process moves to the next area of the sample.

<FIG> is a flowchart showing another exemplary process <NUM> for accelerating digital microscopy scans using artifact and/or dirty area detection. The processor of microscope <NUM> determines whether microscope <NUM> is in a full resolution mode or a partial/empty (PE) mode, at step <NUM>. For example, if microscope <NUM> was scanning in region <NUM> of sample <NUM> of <FIG>, microscope <NUM> would typically employ full resolution imaging. Accordingly, microscope <NUM> may remain in the full resolution mode and assume that data in a next area is of interest. In this regard, the processor may perform an imaging process on that subsequent area at step <NUM>.

The processor may then computationally process the image at step <NUM> to generate a computational image. Generally, a computational image is an image where at least a part of the image was created using a computational process. For example, a computational process may include resolution enhancement and/or quality improvement, such as, aberration correction, computational refocusing, contrast enhancement, distortion correction, color enhancement, registration, and/or removing certain elements of the data such as debris, dust, and/or empty space. Some processes that may be applied to areas that are empty or dirty (e.g., areas <NUM> and <NUM> of <FIG>) include the computational removal of dirt and/or artifacts related to it, full resolution or quality enhancement, partial resolution or quality enhancement, and empty resolution enhancement (e.g., by increasing the pixel count without improving the optical resolving power, also known as interpolation).

In this regard, the processor of microscope <NUM> may perform additional and/or computational imaging processes if the area being observed is also being tested, at step <NUM>. Step <NUM> is an optional step, and can depend on other aspects of the work flow and process <NUM> and other processes and methods as described herein. For example, step <NUM> can be performed when the microscope has identified an area as having relevant data and partially constructed the image as part of step <NUM>. Alternatively, step <NUM> can be skipped, for example when the process comprises the full resolution mode, and process <NUM> has generated the computational image.

Thereafter, the processor may adjust the testing criteria used for testing particular area, at step <NUM>. This may allow the processor to change modes from full resolution mode to PE mode. For example, as the processor is testing an area of the image, the processor may deem the area as either empty or dirty before proceeding to a subsequent area. As a subsequent area may likely be empty or dirty as well, the processor may switch to the PE mode at step <NUM> for the subsequent area. Conversely, if the processor encounters valid data (e.g., a portion of the image occupied by region <NUM> of <FIG>), the processor may be determined that a subsequent region may also comprise valid data. In this regard, the processor may set microscope <NUM> to operate in the full resolution mode at step <NUM>. Although reference is made to the full resolution mode, the full resolution mode may comprise one or more additional or alternative computational processes generally related to the quality of the image, such as aberration correction, etc..

Microscope <NUM> may move on to the next area, at step <NUM>, and returned to step <NUM>. If there is no reason to change the testing criteria (e.g., because the current mode of microscope <NUM> is likely to be used in a subsequent area), the processor may direct microscope <NUM> to simply move on to the next area, at step <NUM>.

Returning to step <NUM>, if the processor determines that microscope <NUM> is operating in the PE mode, the processor may direct microscope <NUM> to perform an imaging process, at step <NUM>. For example, the processor may form a partial imaging of an area and then test whether the area has debris and/or empty space, at step <NUM>. The partial or full imaging partial process may be limited to the computational process, while other processes such as image illumination and acquisition continue. This partial imaging may reduce the computational complexity and thus reduce the number of computations used in the imaging. Then, the processor may determine whether the area includes relevant data or not, at step <NUM>.

If the area does include relevant data, the processor may direct microscope <NUM> to operate in full resolution mode and generate a computational process image, at step <NUM>. Otherwise, the processor may partially process the image or even skip over the entire area, at step <NUM>.

Any of the steps of method <NUM> can be combined with any method step corresponding to a block of workflow <NUM> as described herein. Although workflow <NUM> and method <NUM> are described as a sequence of steps, various concurrent iterations may result in steps being stalled, omitted, repeated, and/or performed in different order. The steps disclosed herein are optional, e.g. steps <NUM> and <NUM>, and can be performed in any order.

As detailed above, the computing devices and systems described and/or illustrated herein broadly represent any type or form of computing device or system capable of executing computer-readable instructions, such as those contained within the modules described herein. In their most basic configuration, these computing device(s) may each comprise at least one memory device and at least one physical processor.

The term "memory" or "memory device," as used herein, generally represents any type or form of volatile or non-volatile storage device or medium capable of storing data and/or computer-readable instructions. In one example, a memory device may store, load, and/or maintain one or more of the modules described herein. Examples of memory devices comprise, without limitation, Random Access Memory (RAM), Read Only Memory (ROM), flash memory, Hard Disk Drives (HDDs), Solid-State Drives (SSDs), optical disk drives, caches, variations or combinations of one or more of the same, or any other suitable storage memory.

In addition, the term "processor" or "physical processor," as used herein, generally refers to any type or form of hardware-implemented processing unit capable of interpreting and/or executing computer-readable instructions. In one example, a physical processor may access and/or modify one or more modules stored in the above-described memory device. Examples of physical processors comprise, without limitation, microprocessors, microcontrollers, Central Processing Units (CPUs), Field-Programmable Gate Arrays (FPGAs) that implement softcore processors, Application-Specific Integrated Circuits (ASICs), portions of one or more of the same, variations or combinations of one or more of the same, or any other suitable physical processor.

Although illustrated as separate elements, the method steps described and/or illustrated herein may represent portions of a single application. In addition, one or more of these steps may represent or correspond to one or more software applications or programs that, when executed by a computing device, may cause the computing device to perform one or more tasks, such as the method step.

In addition, one or more of the devices described herein may transform data, physical devices, and/or representations of physical devices from one form to another. For example, one or more of the devices recited herein may receive image data of a sample to be transformed, transform the image data, output a result of the transformation to determine a 3D process, use the result of the transformation to perform the 3D process, and store the result of the transformation to produce an output image of the sample. Additionally or alternatively, one or more of the modules recited herein may transform a processor, volatile memory, non-volatile memory, and/or any other portion of a physical computing device from one form of computing device to another form of computing device by executing on the computing device, storing data on the computing device, and/or otherwise interacting with the computing device.

The term "computer-readable medium," as used herein, generally refers to any form of device, carrier, or medium capable of storing or carrying computer-readable instructions. Examples of computer-readable media comprise, without limitation, transmission-type media, such as carrier waves, and non-transitory-type media, such as magnetic-storage media (e.g., hard disk drives, tape drives, and floppy disks), optical-storage media (e.g., Compact Disks (CDs), Digital Video Disks (DVDs), and BLU-RAY disks), electronic-storage media (e.g., solid-state drives and flash media), and other distribution systems.

The process parameters and sequence of the steps described and/or illustrated herein are given by way of example only and can be varied as desired. The various exemplary methods described and/or illustrated herein may also omit one or more of the steps described or illustrated herein or comprise additional steps in addition to those disclosed.

The processor as disclosed herein can be configured to perform any one or more steps of a method as disclosed herein.

The preceding description has been provided to enable others skilled in the art to best utilize various aspects of the examples disclosed herein. This exemplary description is not intended to be exhaustive or to be limited to any precise form disclosed.

Claim 1:
A microscope, comprising:
an illumination assembly (<NUM>) operable to illuminate a sample under observation of the microscope;
an image capture device (<NUM>) operable to capture an initial image set of the illuminated sample; and
a processor (<NUM>) coupled to the image capture device (<NUM>);
wherein the illumination assembly (<NUM>) is configured to illuminate the sample at a plurality of illumination conditions, wherein the initial image set comprises a plurality of images, each of the plurality of images corresponding to a different illumination condition, and wherein the plurality of illumination conditions comprises at least one of an illumination angle, an illumination wavelength, an illumination pattern, illumination intensity, or illumination position;
wherein the processor is configured to identify an area of the sample that comprises at least one of artifact or empty space from one or more of the plurality of images; and
wherein the processor is configured to generate a computational image from the plurality of images, and wherein generating the computational image comprises:
operating the processor (<NUM>) in a first mode in response to identifying the area of the sample comprising the at least one of artifact or empty space and in a second mode in response to identifying an area of the sample that does not comprise the at least one of artifact or empty space; and
in the first mode and the second mode, operating the processor (<NUM>) to output portions of the computational image with a first resolution and second resolution, respectively, the first resolution being less than the second resolution.