BrainSpec Core™ software is a post-processing application to analyze and evaluate MR (magnetic resonance) spectroscopy data. It provides evaluation of MR Single Voxel Spectroscopy (SVS) data and MR Chemical Shift Imaging (CSI) data to support the diagnostic process. BrainSpec Core™ software includes the possibility of an integrated reading of MR images and spectroscopy data for spectroscopy exams and focuses on ease-of-use by reducing complexity.

A fit algorithm reduces the need for manual data processing and offers the user reproducible evaluation results. When interpreted by a trained physician, these results provide information that may assist in diagnosis.

The post-processing fits and displays spectra and provides intuitive representations of the metabolic profile. The calculation and display of pre-defined results such as spectral maps, and metabolite images is provided. Interactive reading of spectroscopy exams is supported by side-by-side display of MR images and spectroscopy results. and synchronized display.

Device Description

The BrainSpec Core™ Software provides analysis of magnetic resonance spectroscopy (MRS) data. MRS is a technology available on standard MRI scanners that detects the presence of various chemical compounds in a volume of tissue. The software provides these analyses:

Estimation of the concentrations of various metabolites present in the acquired . data, presented to the user as ratios concentrations (when water reference files is available). These metabolites include N-acetylaspartate (NAA). choline (Cho), creatine (Cr), myoinositol (mlns), and glutamine/glutamate (Glx), DL-lactic acid (Lac), and 2-hydroxygluturate (2HG-ng) expressed as a ratio.
Spatial registration of the acquired volume with anatomical MR images, such that . the spectroscopy volume is overlaid on an anatomical image in the same plane.
. Visual display of the data's spectrum (a representation of the data in which peaks correspond to specific compounds)
. Ratio measurements of each metabolite may be compared to reference percentile data if a reference interval has been established.

BrainSpec Core™ Software supports 3.0 Tesla scanners manufactured by Philips, Siemens, and GE with predefined pulse sequences: PRESS short echo (TE=25-45ms), PRESS (long echo (TE=135-144) and PRESS optimized for 2HG (TE=97).

The software provides a user interface over the web. The user must access the software via the Google Chrome web browser on any operating system, provided the computer has a reliable internet connection. The uploaded data are processed with several applications. Both the web application and the data processing software read and write files and data in Google Cloud Platform resources.

The reference intervals specific for adults indicating how user-uploaded data compares to a range of typical values for a given metabolite ratio are aggregated from decades of data from adult reference subjects with no known history of neurological or major psychiatric disorders. The reference intervals are specific to the acquisition parameters and indicated adult brain region of the uploaded data, and were determined from research studies employing those matching parameters and brain regions. Reference intervals are only displayed when the relevant acquisition parameters are matched.

AI/ML Overview

The provided document is a 510(k) Summary for the BrainSpec Core™ Software. It focuses on demonstrating substantial equivalence to a predicate device and does not contain detailed information about acceptance criteria, a specific study proving the device meets those criteria, or the methodology and results of such a study in the format requested.

Therefore, many of the requested details, such as the specific acceptance criteria values, the reported device performance compared to those criteria, sample sizes for test and training sets, expert qualifications, ground truth establishment, and MRMC study details, cannot be extracted from this document.

However, I can provide the available information:

1. Table of Acceptance Criteria and Reported Device Performance:

The document does not explicitly present a table of acceptance criteria or quantitative reported device performance values. It generally discusses the device's functionality and its comparison to a predicate device without defining specific numerical thresholds for acceptance.

2. Sample size used for the test set and the data provenance:

Test Set Sample Size: Not specified in the document.
Data Provenance: Not specified in the document.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not specified in the document.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

Not specified in the document.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

Not applicable. The document does not describe an MRMC comparative effectiveness study or any human-in-the-loop performance evaluation. The device is a "post-processing application to analyze and evaluate MR (magnetic resonance) spectroscopy data" meant to "support the diagnostic process" and its results are to be "interpreted by a trained physician."

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

The document lists "Valid clinical association" and "Software testing, including unit testing, and verification testing" under "Performance Data," indicating some form of standalone evaluation. However, details of the performance metrics or the specific study for standalone performance are not provided. The phrase "A fit algorithm reduces the need for manual data processing and offers the user reproducible evaluation results" suggests confidence in the algorithm's automated output.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The document mentions that "Reference intervals specific for adults indicating how user-uploaded data compares to a range of typical values for a given metabolite ratio are aggregated from decades of data from adult reference subjects with no known history of neurological or major psychiatric disorders." This suggests that the reference intervals, which aid in interpreting the device's output, are based on aggregated historical data from a healthy population. For the device's core functionality (quantification of metabolites), it states, "Values of metabolite peaks are calculated based on a linear combination" model, which is an algorithmic approach rather than relying on an external ground truth like pathology at the time of calculation.

8. The sample size for the training set:

Not specified in the document.

9. How the ground truth for the training set was established:

Not specified in the document. For the "reference intervals," it states they "were determined from research studies employing those matching parameters and brain regions," but it does not detail how the ground truth for the underlying algorithm's training (if any was used for the "fit algorithm") was established.

Summary of what is available from the document:

The BrainSpec Core™ Software is a post-processing application for MR spectroscopy data, quantifying metabolites like NAA, Cho, Cr, mIns, Glx, Lac, and 2HG. It uses a "fit algorithm" based on a linear combination model for metabolite quantification. The software also provides reference intervals for adult brain regions, aggregated from decades of data from healthy subjects with no known neurological or psychiatric disorders, established according to CLSI guidelines and defined by research studies. The document does not offer a detailed performance study with specific acceptance criteria, sample sizes, expert involvement, or adjudication methods. It primarily focuses on demonstrating substantial equivalence to its predicate device (Siemens Syngo K120315) based on intended use, operating principles, and technological characteristics.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

November 14, 2023

BrainSpec, Inc % Carolyn Guthrie Principal Helix Medical, LLC 711 SE 5th Ave Pompano Beach, Florida 33060

Re: K230856

Trade/Device Name: BrainSpec Core™ Software Regulation Number: 21 CFR 892.2050 Regulation Name: Medical Image Management And Processing System Regulatory Class: Class II Product Code: LLZ, LNI Dated: October 23, 2023 Received: October 24, 2023

Dear Carolyn Guthrie:

We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

{1}------------------------------------------------

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

{2}------------------------------------------------

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

D. Ray Kenned

Daniel M. Krainak, Ph.D. Assistant Director DHT8C: Division of Radiological Imaging and Radiation Therapy Devices OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{3}------------------------------------------------

Indications for Use

510(k) Number (if known) K230856

Device Name BrainSpec Core™ Software

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{4}------------------------------------------------

Image /page/4/Picture/0 description: The image is a logo for Brainspec. The logo features a blue brain outline with a magnifying glass over it, inside the magnifying glass is a white line graph. To the right of the brain is the word "BRAINSPEC" in blue, and below that is the text "MAKING THE VIRTUAL BIOPSY A REALITY" in a smaller font.

510(k) Summary - K230856

In accordance with Title 21 of the Code of Federal Regulations, Part 807, and in particular 21 CFR 807.92, the following summary of information is provided.

Date of Preparation:

November 9, 2023

Applicant

BrainSpec, Inc 111 Speen St, Framingham, MA 01701

Official Correspondent

Carolyn Guthrie Email: cguthrie@helixmedical.us Helix Medical LLC 704-737-2866

Device Name

Trade Name: BrainSpec Core™ Software Common Name: Picture archiving and communications system Regulation Description: System, Image Processing, Radiological Regulation Number: 21 CFR 892.2050 Product Code: LLZ, LNI Classification: Class II Panel: Radiology

{5}------------------------------------------------

Image /page/5/Picture/0 description: The image is a logo for Brainspec. The logo features a blue brain icon with a magnifying glass over it. The magnifying glass is focused on a waveform. Next to the icon is the word "BRAINSPEC" in blue, block letters, and below that is the tagline "MAKING THE VIRTUAL BIOPSY A REALITY" in a smaller, lighter font.

Predicate Devices

BrainSpec Core™ Software is substantially equivalent to the predicate device shown in Table 1.

Trade Name	Clearance	Claim of Equivalence for:	510(k) holder
Siemens Syngo	K120315	Primary Predicate	Siemens
Table 1: Predicate devices

Indications for Use:

Device Description

Estimation of the concentrations of various metabolites present in the acquired . data, presented to the user as ratios concentrations (when water reference files is available). These metabolites include N-acetylaspartate (NAA). choline (Cho), creatine (Cr), myoinositol (mlns), and glutamine/glutamate (Glx), DL-lactic acid (Lac), and 2-hydroxygluturate (2HG-ng) expressed as a ratio.
Spatial registration of the acquired volume with anatomical MR images, such that . the spectroscopy volume is overlaid on an anatomical image in the same plane.

{6}------------------------------------------------

Image /page/6/Picture/1 description: The image is a logo for Brainspec. The logo features a blue brain with a magnifying glass over it, and the word "BRAINSPEC" in blue letters. Below the word "BRAINSPEC" is the phrase "MAKING THE VIRTUAL BIOPSY A REALITY" in smaller, gray letters. The logo is simple and modern, and it conveys the idea of using technology to improve brain health.

. Visual display of the data's spectrum (a representation of the data in which peaks correspond to specific compounds)
. Ratio measurements of each metabolite may be compared to reference percentile data if a reference interval has been established.

Substantial Equivalence

1.1 Comparison of Intended Use

The intended use of BrainSpec Core™ Software is identical to the predicate device.

Features	BrainSpec Core™ Software	syngo.MR Spectroscopy
	Subject Device	Predicate Device
Quantificationof spectra (i.e.,determinationof the intensityof metabolitesignals)	Results are based on a sequenceof post-processing steps; the mainstep is a fit of a metabolite model tothe measured data	Results are based on asequence of post-processingsteps; the main step is a fit of ametabolite model to themeasured data
	Baseline and phase correctionautomatically applied duringmetabolite quantification	No extra step for baseline andphase correction needed
Features	BrainSpec Core™ Software	syngo.MR Spectroscopy
	Subject Device	Predicate Device
	Usage of extended prior knowledgefor the metabolite model(metabolites are represented bytheir model signals, i.e., theircomplete spectral pattern)	Usage of extended priorknowledge for the metabolitemodel (metabolites arerepresented by their modelsignals, i.e., their completespectral pattern)
	Spectral quality check performed,with additional metrics for dataquality and metabolite fits	Spectral quality checkperformed
Handling ofspectroscopyresults	Support of spectra, result tables,metabolite images, spectral maps,and image co-registration	Support of spectra, result tables,metabolite images, spectralmaps, and reference images
	Interactive modification of displaycharacteristics of spectro results(e.g., toggle fit and baselinedisplay, add or remove metaboliteratios, and transparency for ametabolite image)	Interactive modification ofdisplay characteristics of spectroresults (e.g., adjusting the rangeand scale for a spectrum,adjusting the range andtransparency for a metaboliteimage)
	Interactive voxel selection onmetabolite map and co-registrationimages with automatic update ofspectrum display	Interactive voxel selection onmetabolite- and referenceimages with automatic update ofspectrum display
	Interactive voxel selection onmetabolite map and co-registrationimages with automatic update ofspectrum display	Synchronized scrolling throughreference and metaboliteimages with automatic update ofspectrum display
	Display of measurementparameters	Display of measurementparameters
	Display of measurementparameters as image test	Display of measurementparameters as image test
Features	BrainSpec Core™ Software	syngo.MR Spectroscopy
	Subject Device	Predicate Device
	Saving of spectro results in a PDF report for off-line viewing	Saving of spectro results as screenshots and their usage for printing
	Image co-registration available	Usage of reference images of arbitrary orientations with respect to the CSI slab possible (MPR creation for reference images)
	Visualization of default spectra	Visualization of default spectra
Usage of post processing protocols for spectroscopy	All relevant parameters for post-processing and display contained	All relevant parameters for post-processing and display contained
	Dedicated protocols for typical measurement scenarios	Dedicated protocols for typical measurement scenarios
	Automatic protocol selection	Automatic protocol selection
Usage of standardized enhanced DICOM format “MR spectroscopy object” for spectro raw data	Yes	Yes
Hardware prerequisites	Software only device	Software only device

1.2 Comparison of Operating Principle

{7}------------------------------------------------

Image /page/7/Picture/1 description: The image is a logo for Brainspec. The logo features a blue brain icon with a magnifying glass over it on the left side. To the right of the icon, the word "BRAINSPEC" is written in blue, block letters. Below the company name is the phrase "MAKING THE VIRTUAL BIOPSY A REALITY".

{8}------------------------------------------------

Image /page/8/Picture/1 description: The image is a logo for Brainspec. The logo features a blue brain outline with a magnifying glass over it, and the word "BRAINSPEC" in blue, block letters. Below the word "BRAINSPEC" is the tagline "MAKING THE VIRTUAL BIOPSY A REALITY" in a smaller, lighter font.

1.3 Comparison of Technological Characteristics with the Predicate Device

Feature	Subject Device	syngo.MR Spectroscopy	Discussion of differences
Quantificationof spectra (i.e.,determinationof the intensity	Quantification ofthe followingmetabolites:NAA, Ins, Cho,	Quantification ofthe followingmetabolites:	2HG is a metabolite quantifiedby the subject device but not bythe predicate.
Feature	Subject Device	syngo.MRSpectroscopy	Discussion of differences
of metabolitesignals)	Cr, Glx, Lac,2HG	NAA, Ins, Cho,Cr, Glx, Lac	It is quantified in the samemanner (algorithm) as the othermetabolites but with differentacquisition parameters.
	Values ofmetabolite peaksare calculatedbased on alinearcombination	Integral values ofmetabolite peaksare calculatedbased on the fitresults	The linear combination modelapproach to metabolitequantification improves on peakintegration methods byincorporating prior knowledgeof the metabolite peaks for agiven pulse sequence and echotime. It allows for modeling ofbaseline and macromoleculecontributions, which otherwisecreate artifacts in the spectrumthat cannot be easily accountedfor using peak integration. Bothmethods of quantification resultin metabolite values / ratios.
Handling ofspectroscopyresults	Display ofquantificationwithin areferenceinterval for ametabolite withina brain region, ifavailable	Comparison ofspectro results ofdifferentmeasurements ofone and morepatients	Use of reference intervals inthe BrainSpec Core™ softwaredoes not alter the quantificationof the metabolite. The intervalswere established according toCLSI guidelines and areintended to provide furthersupport in the diagnosticprocess.
	Feature notincluded	3D scaling ofmetaboliteimages andspectral maps	3D scaling in the predicateallows for an alternative view ofthe imaging and spectra. Thisdoes not alter the method forquantification and thereforedoes not impact the intendeduse of the device.
	Feature notincluded	Real-timespectrum update(real timeupdates of thespectrum withoutmouse clicking)	Data is processed in theBrainSpec Core™ softwareafter spectra are acquired. Lackof an "on the fly" update doesnot introduce any questions ofsafety or effectiveness.
Feature	Subject Device	syngo.MR Spectroscopy	Discussion of differences
Usage of post processing protocols for spectroscopy	Feature not included	("on-the-fly" display)User-configurable protocols	Only preset acquisition protocols are supported to limit the conditions to the tested environment.
Software prerequisites	Google Chrome version v79 or higher	Windows XP or Windows Vista	Use of a cloud-based service introduces cybersecurity concerns vs a non-wired software. Cybersecurity controls are in place to reduce the risk associated with cybersecurity.
RIS Communication	Feature not included	Yes	Reporting output does not relate to safety or performance, and is therefore considered an acceptable difference

{9}------------------------------------------------

Image /page/9/Picture/1 description: The image is a logo for Brainspec. The logo features a blue brain icon with a magnifying glass over it, and a waveform inside the magnifying glass. To the right of the icon is the word "BRAINSPEC" in blue, with the tagline "MAKING THE VIRTUAL BIOPSY A REALITY" in gray below it.

{10}------------------------------------------------

Image /page/10/Picture/0 description: The image is a logo for Brainspec. The logo features a blue brain silhouette with a magnifying glass over it, and a white line graph inside the magnifying glass. To the right of the brain is the word "BRAINSPEC" in blue, and below that is the phrase "MAKING THE VIRTUAL BIOPSY A REALITY" in a smaller font.

Performance Data

The following information is provided in support of substantial equivalence.

. Valid clinical association
Risk Management activities
Software testing, including unit testing, and verification testing ●
Off-the-Shelf software analysis
Cybersecurity assessment ●

11 Conclusion

BrainSpec Core™ Software and the predicate device Siemens Syngo (K120315) have the same intended use and are available by prescription only. Any technical differences identified do not result in new questions of safety or effectiveness.

Through assessment of technological characteristics, intended use and performance data, it can be concluded that BrainSpec Core™ Software is substantially equivalent to the Siemens Syngo device.

Regulation Number and Section

§ 892.2050 Medical image management and processing system.

(a)
Identification. A medical image management and processing system is a device that provides one or more capabilities relating to the review and digital processing of medical images for the purposes of interpretation by a trained practitioner of disease detection, diagnosis, or patient management. The software components may provide advanced or complex image processing functions for image manipulation, enhancement, or quantification that are intended for use in the interpretation and analysis of medical images. Advanced image manipulation functions may include image segmentation, multimodality image registration, or 3D visualization. Complex quantitative functions may include semi-automated measurements or time-series measurements.(b)
Classification. Class II (special controls; voluntary standards—Digital Imaging and Communications in Medicine (DICOM) Std., Joint Photographic Experts Group (JPEG) Std., Society of Motion Picture and Television Engineers (SMPTE) Test Pattern).