(462 days)
The text states that "Reference Device(s): Not Found". Therefore, there are no reference devices K/DEN numbers to list from the provided text.
No
The summary does not mention AI, DNN, or ML, and the performance studies describe traditional statistical methods and comparisons to predicate devices and other modalities like DXA, rather than validation of AI/ML model performance.
No
The device is a diagnostic tool that provides information to physicians to assess fracture risk and identify osteoporosis; it does not directly treat or provide therapy to patients.
Yes
Explanation: The "Intended Use / Indications for Use" section states that the information provided by VirtuOst "can be used by a physician to assess fracture risk, identify osteoporosis, and monitor therapy," which are diagnostic purposes. The "Device Description" also reiterates that "VirtuOst measurements can be used by a physician to identify osteoporosis, assess fracture risk, and monitor therapy."
Yes
The device description explicitly states "VirtuOst is a software-only medical device". The description of its function, analyzing existing CT scan data, further supports this.
Based on the provided information, VirtuOst is not an In Vitro Diagnostic (IVD).
Here's why:
- IVDs analyze biological samples: In Vitro Diagnostics are devices used to examine specimens derived from the human body, such as blood, urine, or tissue, outside of the body.
- VirtuOst analyzes medical images: VirtuOst analyzes data from computed tomography (CT) scans, which are medical images of the body, not biological samples.
- The intended use and device description focus on image analysis: The description clearly states that VirtuOst "analyzes data in computed tomography (CT) scans" to estimate bone properties.
Therefore, VirtuOst falls under the category of a medical device that performs image analysis for diagnostic purposes, but it does not meet the definition of an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
VirtuOst uses data from computed tomography scans to estimate bone mineral density, bone strength, and a load-to-strength ratio. This information can be used by a physician to assess fracture risk, identify osteoporosis, and monitor therapy. For pediatric patients, VirtuOst provides these estimates without any classifications and should be used only when the benefit of obtaining these estimates outweighs the risk of radiation.
Product codes
KGI
Device Description
VirtuOst is a software-only medical device that analyzes data in computed tomography (CT) scans to measure bone mineral density (BMD), bone strength, and a load-to-strength ratio at the proximal femur and vertebral body. BMD is measured from both a 2D projection (in g/cm2) and a volumetric scan reconstruction (in mg/cm³) of the CT scan. VirtuOst measurements can be used by a physician to identify osteoporosis, assess fracture risk, and monitor therapy. The VirtuOst analysis is performed on previously physician-acquired image data and is unrelated to acquisition equipment and clinical workstations.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Computed Tomography (CT) scans
Anatomical Site
proximal femur and vertebral body (at least one complete vertebra from T1-L5)
Indicated Patient Age Range
Not Found (Explicitly mentions "For pediatric patients" and "324 women and men age 48-85" in performance studies, but no definitive range is given for the overall indication)
Intended User / Care Setting
Physician / Radiology (Implied by PACS integration)
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Hip areal BMD (in g/cm²):
- Sample size: 324 women and men
- Data source: Paired CT and DXA images obtained from 324 women and men age 48-85.
- Annotation protocol: Not explicitly defined as annotation. BMD was measured at the femoral neck and total hip using the subject device and DXA. For the subject device, these measurements were then converted into DXA-equivalent values.
Phantomless Calibration:
- Data source for reference data for visceral fat attenuation: 268 patients scanned on 31 different CT scanners, plus scans of a custom torso phantom consisting of various tissue-equivalent chambers and scanned on 35 different CT scanners. Scanners were from the four major CT manufacturers (GE Healthcare. Siemens Medical Solutions, Philips Healthcare and Toshiba International) at various settings (80-140 kVp).
- Test Set Sample size: 40 independent patient CT scans.
- Annotation protocol: For 40 independent patient CT scans, femoral strength and BMD were then compared for fat/air phantomless calibration versus phantom calibration (external calibration phantom, a reference standard).
CT-to-DXA areal BMD conversion for the hip (used when calculating T- and Z-scores):
- Sample size: 200 subjects
- Data source: 200 subjects scanned on both CT and DXA.
- Annotation protocol: The conversion equations were formulated from regression analysis of the paired CT and DXA areal BMD measurements, separately by sex and for the femoral neck, total hip, and trochanter.
Slice spacing adjustment for femurs:
- Data source: Pairs of CT images, one thin and thick reconstruction in each pair.
- Annotation protocol: Linear regression analysis was used to develop adjustments.
- Observational study for hip fracture prediction: 2,783 women and men (1,306 with hip fracture; case-cohort study design).
Non-clinical tests:
- Automated unit and regression testing.
- Manual component testing (i.e. black box testing).
- Each test includes preconditions for testing, test steps, an expected result, an observed result and a pass/fail determination.
- Tests included: exercising each functionality of the worklist module, verifying new input types (coronal and compressed images), verifying modified femoral head segmentation, verifying fat/air calibration, verifying slice spacing adjustments, verifying range checks, verifying results report elements, and verifying DICOM results objects.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Hip areal BMD (in g/cm²):
- Study type: Comparison to FDA-cleared DXA devices (reference standard).
- Sample size: 324 women and men age 48-85.
- Key results: Variance between femoral neck areal BMD measurements was acceptable (standard error of the regression of 0.048 g/cm² was below the highest pre-specified acceptable value of ≤ 0.051 g/cm²). Stratified results for women (0.044 g/cm², N=244) and men (0.051 g/cm², N=80) were also acceptable.
Phantomless Calibration:
- Study type: Comparison of fat/air phantomless calibration versus phantom calibration.
- Sample size: Reference data from 268 patients and 35 phantom scans; main comparison study with 40 independent patient CT scans.
- Key results: Mean values of measurements using the two calibration methods were not significantly different (p>0.05) and showed a high degree of agreement (R² = 0.98-0.99) with no fixed or proportional bias.
CT-to-DXA areal BMD conversion for the hip (used when calculating T- and Z-scores):
- Study type: Regression analysis to formulate sex-specific conversion equations.
- Sample size: 200 subjects.
- Key results: The standard errors for the new equations ranged from 0.025-0.047 g/cm² and were thus considered acceptable (below the acceptance criterion of 0.051 g/cm²).
Slice spacing adjustment for femurs:
- Study type: Paired CT image analysis for adjustment development, followed by an observational study of hip fractures.
- Sample size: Not specified for the paired image analysis; 2,783 women and men for the observational study (1,306 with hip fracture).
- Key results: Measurements from images with thin and thick slice spacing were highly correlated (R > 0.98). Hazard ratios for hip fracture using femoral strength or hip areal BMD from VirtuOst were at least as good as hip areal BMD from DXA. No evidence of a slice spacing effect on these results.
Non-clinical tests:
- Study type: Verification and validation testing (automated unit and regression testing, manual component testing/black box testing).
- Sample size: Not applicable in terms of patient numbers.
- Key results: Tests ensured that software requirements are met and that the device performs as intended, with all tests passing.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Standard error of the regression: 0.048 g/cm² (femoral neck areal BMD), 0.044 g/cm² (women), 0.051 g/cm² (men), 0.025-0.047 g/cm² (CT-to-DXA conversion).
- p-value: >0.05 (Phantomless Calibration)
- R²: 0.98-0.99 (Phantomless Calibration)
- R: >0.98 (Slice Spacing for femurs)
- Hazard ratios: "at least as good as hip areal BMD from DXA" (Slice Spacing for femurs)
Predicate Device(s)
VirtuOst – K113725
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 892.1170 Bone densitometer.
(a)
Identification. A bone densitometer is a device intended for medical purposes to measure bone density and mineral content by x-ray or gamma ray transmission measurements through the bone and adjacent tissues. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II.
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May 19, 2023
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA text logo on the right. The text logo is in blue and reads "FDA U.S. FOOD & DRUG ADMINISTRATION" in a sans-serif font. The FDA logo is a recognizable symbol of the agency's role in protecting public health.
O.N. Diagnostics % David Kopperdahl Director, Research and Development 1936 University Ave., Suite 280 BERKELEY.CA 94704
Re: K220402
Trade/Device Name: VirtuOst Regulation Number: 21 CFR 892.1170 Regulation Name: Bone Densitometer Regulatory Class: Class II Product Code: KGI Dated: April 19, 2023 Received: April 19, 2023
Dear David Kopperdahl:
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 (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 located 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.
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 803) for
1
devices or postmarketing safety reporting (21 CFR 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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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.
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.
Lu Jiang
Lu Jiang, Ph.D. Assistant Director Diagnostic X-ray Systems Team DHT8B: Division of Radiological Imaging Devices and Electronic Products OHT8: Office of Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name
VirtuOst
Indications for Use (Describe)
VirtuOst uses data from computed tomography scans to estimate bone mineral density, bone strength, and a load-tostrength ratio. This information can be used by a physician to assess fracture risk, identify osteoporosis, and monitor therapy. For pediatric patients, VirtuOst provides these without any classifications and should be used only when the benefit of obtaining these estimates outweighs the risk of radiation.
| 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) |
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510(K) SUMMARY
| Date: | May 18, 2023 |
|---|---|
| 510(k) Number: | K220402 |
| 1) Applicant Information | |
| 510(k) Owner: | O.N. Diagnostics, LLC |
| 1936 University Ave. Suite 280 | |
| Berkeley, CA 94704 | |
| Contact Person: | David L. Kopperdahl, PhD |
| Director, Research and Development | |
| O.N. Diagnostics, LLC | |
| 1936 University Avenue, Suite 280 | |
| Berkeley, CA 94704 | |
| Phone 510-204-0688 | |
| Fax 510-356-4349 | |
| Establishment Reg. No.: | 3010687441 |
2) Device Identification
| Trade Name: | VirtuOst | |
|---|---|---|
| Common Name: | QCT Bone Densitometer | |
| Regulation Number: | 21 CFR 892.1170 | |
| Regulation Name: | Bone Densitometer | |
| Regulatory Class: | II | |
| Product Code: | KGI |
3) Predicate Device
| Trade Name: | VirtuOst – K113725 |
|---|---|
| Common Name: | QCT Bone Densitometer |
| Regulation Number: | 21 CFR 892.1170 |
| Regulation Name: | Bone Densitometer |
| Regulatory Class: | II |
| Product Code: | KGI |
4) Device Description
VirtuOst is a software-only medical device that analyzes data in computed tomography (CT) scans to measure bone mineral density (BMD), bone strength, and a load-to-strength ratio at the proximal femur and vertebral body. BMD is measured from both a 2D projection (in g/cm2) and a volumetric scan reconstruction (in mg/cm³) of the CT scan. VirtuOst measurements can be
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used by a physician to identify osteoporosis, assess fracture risk, and monitor therapy.
The VirtuOst analysis is performed on previously physician-acquired image data and is unrelated to acquisition equipment and clinical workstations.
5) Intended Use
VirtuOst uses data from computed tomography scans to estimate bone mineral density, bone strength, and a load-to-strength ratio. This information can be used by a physician to assess fracture risk, identify osteoporosis, and monitor therapy.
6) Indications for Use
VirtuOst uses data from computed tomography scans to estimate bone mineral density, bone strength, and a load-to-strength ratio. This information can be used by a physician to assess fracture risk, identify osteoporosis, and monitor therapy. For pediatric patients, VirtuOst provides these estimates without any classifications and should be used only when the benefit of obtaining these estimates outweighs the risk of radiation.
7) Substantial Equivalence
This 510(k) premarket notification is an application to the FDA to modify VirtuOst. a class II software medical. The predicate device is the version of VirtuOst initially cleared in 2012 (K113725); the subject device is a modified version of VirtuOst. The subject and predicate devices both estimate bone mineral density, bone strength and a load-to-strength ratio using a computed tomography scan as input. Compared to the predicate device, the subject device includes several modifications, none of which affected the performance of the VirtuOst in terms of safety or effectiveness. A risk analysis was performed evaluating the effects of the device modifications on patient safety, and no new hazards were introduced. Functional black box tests and a regression test were used to verify that the functionality of and outputs from VirtuOst have remained consistent across software releases. Performance data are presented demonstrating no substantial changes in technical characteristics for the safety or effectiveness of VirtuOst.
| Summary of Technology Characteristics and Comparison with Predicate Device | ||
|---|---|---|
| Device | ||
| Characteristic | Predicate Device (K113725) | Subject Device (K220402) |
| Trade Name | VirtuOst | No change. |
| Version | 1.2.1 | 2.5.0b |
| Device | ||
| Characteristic | Predicate Device (K113725) | Subject Device (K220402) |
| Product Code | KGI | KGI |
| Device | ||
| Classification | Class II | No change. |
| Construction | Software application coded primarily | |
| in Python, C and C++. | No change. | |
| Intended Use | VirtuOst uses data from computed | |
| tomography scans to estimate bone | ||
| mineral density, bone strength, and a | ||
| load-to-strength ratio. This | ||
| information can be used by a | ||
| physician to assess fracture risk, | ||
| identify osteoporosis, and monitor | ||
| therapy. | No change. | |
| Indications for Use | VirtuOst uses data from computed | |
| tomography scans to estimate bone | ||
| mineral density, bone strength, and a | ||
| load-to-strength ratio. This | ||
| information can be used by a | ||
| physician to assess fracture risk, | ||
| identify osteoporosis, and monitor | ||
| therapy. For pediatric patients, | ||
| VirtuOst provides these estimates | ||
| without any classifications and | ||
| should be used only when the benefit | ||
| of obtaining these estimates | ||
| outweighs the risk of radiation. | No change. | |
| Worklist | None. | A worklist organizes and tracks the |
| status of VirtuOst jobs and can be | ||
| populated from a PACS-driven | ||
| modality worklist. | ||
| Device | ||
| Characteristic | Predicate Device (K113725) | Subject Device (K220402) |
| Required Input | A. Computed tomography scan with adequate coverage of the hip (at least one proximal femur) or the spine (at least one complete vertebra from T1-L5). | |
| B. The CT scan must be an uncompressed transverse reconstruction. | A. Computed tomography scan with adequate coverage of the hip (at least one proximal femur) or the spine (at least one complete vertebra from T1-L5). | |
| B. The CT scan can be uncompressed or compressed, and the slice orientation can be transverse, sagittal, or coronal. | ||
| Bone segmentation | Vertebra: | |
| 3D active contour segmentation. |
Femur:
Slice-by-slice manual 2D active contour segmentation. | Vertebra:
3D active contour segmentation.
Femur:
Slice-by-slice semi-automated 2D active contour segmentation with 3D segmentation of the femoral head. |
| Phantom calibration | Uses an external calibration phantom | No change |
| Phantomless
calibration | Utilizes blood and air from the patient's CT scan. | Utilizes blood and air, or fat and air, from the patient's CT scan. |
| Slice spacing
adjustment for
femurs | No adjustment. | An adjustment is applied to BMD and strength measurements for CT scans having a slice spacing greater than 3mm. |
| Reported
measurements and
classifications from
a hip analysis | Femoral strength Femoral neck areal BMD Total hip areal BMD BMD T- and Z-scores Strength classification BMD classification Load-to-strength ratio | No change. |
| Device
Characteristic | Predicate Device (K113725) | Subject Device (K220402) |
| Reported
measurements and
classifications from
a spine analysis | Vertebral strength Vertebral trabecular BMD BMD Z-score Load-to-strength ratio For levels T12-L3: Strength classification BMD classification | No change. |
| Hip areal BMD (in
g/cm²) | Reported VirtuOst values are
converted to be equivalent to Hologic
DXA values. | Reported VirtuOst values are not
converted and may differ from
Hologic DXA values. |
| CT-to-DXA areal
BMD conversion for
the hip (used when
calculating T- and
Z-scores) | One equation for women and men. | Separate equations for women and
men. |
| Hip areal BMD
T-and Z-scores for
diagnostic purposes
using W.H.O.
criteria | DXA-equivalent and NHANES
compatible. | No change. |
| Overall fracture risk
classification | Based on the worst (highest risk)
classification for strength or BMD at
the hip or spine. | No change. |
| Bone images on the
results report | Greyscale projections showing BMD
distribution and regions of interest for
measuring BMD.
Images are labeled "not for diagnostic
use." | Greyscale projections showing BMD
distribution and regions of interest for
measuring BMD.
Images are labeled "not for diagnostic
use."
Color images of the finite element
model under virtual loading. |
| Strength vs. age
plots on the results
report | Plots are shown for bone mineral
density versus age. | Plots are shown for bone mineral
density versus age.
Plots are shown for strength versus
age. |
| Device
Characteristic | Predicate Device (K113725) | Subject Device (K220402) |
| Automated range
check | None. | Range checks are automatically
calculated for multiple parameters
and outlier values are identified.
When a parameter is flagged, the
technologist is prompted to review
the CT scan for artifacts and the
analysis procedure for errors. |
| Output file format
for results | pdf | pdf
DICOM encapsulated pdf
DICOM structured report
DICOM secondary capture image |
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For any technological characteristics that have been modified, none of the modifications substantially affect the safety or effectiveness of the medical device, as discussed below.
Worklist: A worklist organizes and tracks the status of VirtuOst jobs and can be populated from a PACS-driven modality worklist. This functionality improves workflow efficiency, reduces user input errors, and enables integration with other Radiology systems. This modification does not substantially affect the safety or effectiveness of the medical device.
Required input: VirtuOst can now open compressed CT scans, and the slice orientation can be transverse, sagittal, or coronal instead of just transverse. This change increases throughput by allowing VirtuOst to run on more types of CT images without the need to create an additional reconstruction if the image is not an uncompressed transverse reconstruction. This modification does not substantially affect the safety or effectiveness of the medical device.
Bone segmentation: A refinement of the femur segmentation increases throughput compared to the predicate. A technician still reviews all segmentations and adjusts if necessary. This modification does not substantially affect the safety or effectiveness of the device.
Phantomless Calibration: Adipose tissue is added as an option for phantomless calibration. For phantomless calibration, the predicate device measures the attenuation of aortic blood and air outside of the patient. However. CT scans taken with intravenous contrast are not suitable for this type of phantomless calibration because the contrast agent can appreciably alter the attenuation of the blood. Further, the measurement of blood might sometimes be unreliable due to a small volume of interest or local image artifacts from an aortic stent or calcification. The modified device enables adipose tissue instead of blood to be used for the phantomless calibration. Performance data shows fat-air calibration, like the predicate device blood-air calibration, is equivalent to using phantom-based calibration (which uses an external calibration phantom). Thus, this modification does not substantially affect the safety or effectiveness of the device.
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Slice spacing adjustment for femurs: Measurements of strength and areal BMD at the hip can be slightly lower when measured from CT images reconstructed with large (> 3 mm) slice spacing compared to thinner slice spacing. To account for this, for CT scans having a slice spacing of greater than 3 mm, VirtuOst now applies an adjustment to the strength and areal BMD measurement values at the hip. This adjustment provides measurements that are equivalent to those from 1.25 mm scans. Performance data confirmed that this modification produced measurements with better agreement between thin- and thick-slice images. This modification does not substantially affect the safety or effectiveness of the device.
Hip areal BMD (in g/cm'): Due to its 2D nature, DXA technology makes limiting assumptions about the patient's soft tissue surrounding the bone in order to measure BMD. As a result, two patients with the same true bone density but different body compositions can have different areal BMD measurements from DXA. This limitation is absent from CT-measured areal BMD by VirtuOst, which virtually removes all soft tissue in 3D before projecting the bone image. The predicate device reported hip BMD values after their conversion to a DXA-equivalent value. The modified device instead reports the CT-measured areal BMD before this conversion. However, when calculating BMD T- and Z-scores, a CT-to-DXA conversion is still applied in VirtuOst before using any DXA-based reference data (such as NHANES) so that the resulting T- and Z-scores from VirtuOst remain DXA-equivalent. Because the T- and Z-scores (and not the values of BMD) are used to identify osteoporosis and assess fracture risk, this modification does not substantially affect the safety or effectiveness of the device.
CT-to-DXA areal BMD conversion for the hip (used when calculating T- and Z-scores): The CT-to-DXA conversion equations for hip areal BMD measurements were refined to make them sex-specific, due in part to the limitations noted above for DXA because body composition typically differs between the sexes. As with the predicate device, the CT-to-DXA conversion equations are used in the subject device to make the hip areal BMD T - and Z-scores from VirtuOst be equivalent to those from DXA. Because the T- and Z-scores are used to identify osteoporosis and assess fracture risk, this modification does not substantially affect the safety or effectiveness of the device.
Bone images on the results report: Images of the finite element models showing the virtual loading in the stress analysis are now shown on the results report. As with the images showing bone density, all images are labeled "not for diagnostic use." These images help the physician and patient better understand the strength results. This modification does not substantially affect the safety or effectiveness of the device.
Strength vs. age plots on the results report: Images showing femoral strength and vertebral strength vs. age are shown on the results reports. Unlike BMD, Z-scores are not reported for strength measurements, thus the data in these plots are not used in the calculation of an outcome parameter. The plots provide information on how strength changes with age, which can aid interpretation of the strength measurements. This modification does not substantially affect the safety or effectiveness of the device.
Automated range check: During a VirtuOst analysis, range checks are automatically calculated for multiple parameters and outlier values are identified. When a parameter is flagged, the technologist is prompted to review the CT scan for artifacts and the analysis procedure for errors. The technologist must respond to the prompt in order to proceed with the analysis. This
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modification helps to reduce user errors and improves throughput by detecting potential problems earlier in the analysis. This modification does not substantially affect the safety or effectiveness of the device.
Output file format for results: The results report can be provided in several DICOM formats to improve workflow efficiency and facilitate VirtuOst results being received and read by other Radiology applications such as PACS. This modification does not substantially affect the safety or effectiveness of the device.
Summary of Clinical and Non-Clinical Performance Data
Hip areal BMD (in g/cm): Areal BMD measurements for the modified device were compared to those for multiple types of FDA-cleared DXA devices in use in clinical practice, which together served as a reference standard. Paired CT and DXA images were obtained from 324 women and men age 48-85. BMD was measured at the femoral neck and total hip using the subject device and DXA. For the subject device, these measurements were then converted into DXA-equivalent values. Variance between femoral neck areal BMD measurements was acceptable (standard error of the regression of 0.048 g/cm- was below the highest pre-specified acceptable value of ≤ 0.051 g/cm-). Stratified results for the women (0.044 g/cm-, N=244) and men (0.051 g/cm², N=80) were also acceptable. These data demonstrate substantial equivalence of the hip areal BMD measurements for the modified device compared to DXA, a clinical reference standard.
Phantomless Calibration: Phantomless calibration using visceral fat is described. Utilizing visceral fat allows phantomless calibration when aortic blood is not available (such as with scans enhanced with intra-venous contrast). The reference data for visceral fat attenuation was derived from 268 patients scanned on 31 different CT scanners, plus scans of a custom torso phantom consisting of various tissue-equivalent chambers and scanned on 35 different CT scanners. Scanners were from the four major CT manufacturers (GE Healthcare. Siemens Medical Solutions, Philips Healthcare and Toshiba International) at various settings (80-140 k Vp). For 40 independent patient CT scans, femoral strength and BMD were then compared for fat/air phantomless calibration versus phantom calibration (external calibration phantom, a reference standard). Mean values of measurements using the two calibration methods were not significantly different (p>0.05) and showed a high degree of agreement (R2 = 0.98-0.99) with no fixed or proportional bias. These results indicate that phantomless calibration using visceral fat is substantially equivalent to calibration using an external calibration phantom and therefore does not substantially affect the safety or effectiveness of VirtuOst.
CT-to-DXA areal BMD conversion for the hip (used when calculating T- and Z-scores):
VirtuOst applies a CT-to-DXA conversion to hip areal BMD measurements to enable the use of the NHANES normative reference data for the calculation of T- and Z-scores. In the modified device, the equations were updated and made sex-specific using data from 200 subjects scanned on both CT and DXA. The conversion equations were formulated from regression analysis of the paired CT and DXA areal BMD measurements, separately by sex and for the femoral neck, total hip, and trochanter. Following the acceptance criterion used for the predicate device, the
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acceptance criterion was a standard error of the regression of less than 0.051 g/cm². The standard errors for the new equations ranged from 0.025-0.047 g/cm² and were thus considered acceptable.
Slice spacing adjustment for femurs: Using pairs of CT images, slice spacing adjustments were developed for femoral strength and areal BMD from the femoral neck, trochanteric, and total hip regions. Each image pair contained one thin and thick reconstruction. Measurements from images with thin and thick slice spacing were highly correlated (R > 0.98). Linear regression analysis was used to develop adjustments so that measurements from images with a slice spacing greater than 3 mm are equivalent to measurements from images with a slice spacing of 1.25 mm. The modified device was since used in an observational study of hip fractures in which hip fracture prediction was compared between VirtuOst and DXA for 2,783 women and men (1,306 with hip fracture; case-cohort study design). Hazard ratios for hip fracture using femoral strength or hip areal BMD from VirtuOst were at least as good as hip areal BMD from DXA. Moreover, there was no evidence of a slice spacing effect on these results. Thus, we conclude that the slice spacing adjustment did not substantially affect the safety or effectiveness of VirtuOst.
Non-clinical tests: Verification and validation testing was also performed for all non-clinical modifications to the device. These tests, following best practices for software development, included automated unit and regression testing as well as manual component testing (i.e. black box testing). These tests ensure that software requirements are met, and that the device performs as intended. Each test includes preconditions for testing, test steps, an expected result, an observed result and a pass/fail determination. Tests included exercising each functionality of the worklist module such as loading jobs from the list and pulling CT scans from PACS; verifying that new inputs such as coronal and compressed images can be loaded, reconstructed and analyzed to obtain correct results; verifying that the modified femoral head segmentation completes and produces an appropriate segmentation mask; verifying that the fat/air calibration produces the expected calibration coefficients; verifying that slice spacing adjustments are applied correctly to scans of various spacing; verifying that the range checks correctly identify outliers as expected; verifying that all elements of the results report are present and display correctly such as the images of the finite element models and strength vs. age plots; and verifying that the DICOM results objects are correctly formatted and can be read and displayed by a DICOM compliant application entity. These non-clinical tests verified that the subject device met expected performance standards.
8) Conclusion
The subject device VirtuOst is a modified version of the predicate device, VirtuOst (K113725). The modifications to VirtuOst do not involve any change in the intended use or indications for use. Risk analysis and performance data together indicate that the modifications to VirtuOst have not substantially altered safety or effectiveness. O.N. Diagnostics believes, that subject device VirtuOst remains substantially equivalent to the predicate device.