ANATOMAGE CR001 01/24/13 Rev. B

Clinical Evaluation Report: Literature Review

Author Thomas Navarro, RAC

January 2013 Page 1 of 18

InvivoDental / TxStudio

Clinical Evaluation Report:

Literature Review

Reviewed by: Signature Date

Mike Mendez, Quality Manager

Approved by: Signature Date

Dr. James Mah, Literature Appraiser

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Clinical Evaluation Report: Literature Review

Author Thomas Navarro, RAC

January 2013 Page 2 of 18

Table of Contents

1. General Details ............................................................................................................................ 3 Manufacturer ........................................................................................................................... 3

Product Description, Code and Classification .......................................................................... 3 2. Device Description and Indication for Use ................................................................................... 3

Device Description .................................................................................................................. 3 Intended Use, Indications for Use and Claims .......................................................................... 3

3. Clinical Evaluation....................................................................................................................... 4 4. Context of Literature Review ....................................................................................................... 4

Purpose of the Review ............................................................................................................. 4 Search Strategy ........................................................................................................................ 4

Search Results ......................................................................................................................... 5 5. Data Appraisal ............................................................................................................................. 6

Review of Relevant Published Literature ................................................................................. 6 Peer-reviewed Articles related to Radiological Image Processing Systems ............................... 6

Case Studies related to Anatomage Invivo Dental software .................................................... 10 Editorials and Expert Opinions .............................................................................................. 14

Other Relevant Articles of Interest ......................................................................................... 15 Evaluation of Adverse Reports from FDA MAUDE database ................................................ 16

6. Data Analysis ............................................................................................................................. 17 Performance .......................................................................................................................... 17

Safety .................................................................................................................................... 17 7. Conclusions ............................................................................................................................... 17

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Clinical Evaluation Report: Literature Review

Author Thomas Navarro, RAC

January 2013 Page 3 of 18

1. General Details

Manufacturer

Anatomage, Inc.

111 N. Market Street

Suite 800

San Jose, California, U.S.A.

Product Description, Code and Classification

Product Name: InvivoDental/TxStudio software

Product Code: LLZ

Product Classification: Class IIa (EU) Class II (US)

2. Device Description and Indication for Use

Device Description

InvivoDental/TxStudio is dental imaging software that enables doctors to create three-dimensional

(3D) volume renderings on their own computers; get cross-sections, trace nerves, place implants, print

images, save images, and many more functions. The software is designed to reconstruct these 3D

volume renderings from DICOM files generated by cone-beam computed tomography (CBCT),

medical computerized tomography (CT), and MRI radiography machines.

Anatomage InvivoDental was first cleared for marketing in the United States on April 6, 2007, under

the premarket 510(k) application K070803. This Class II software product was found to be

substantially equivalent to similar products such as Materialise SimPlant System (K033489),

Cybermed Vimplant (K053155) and Implant Logic VIP System (K060267).

An EC Certificate was initially issued by our Notified Body AMTAC (Intertek) for full quality

assurance system under the MDD Directive 93/42/EEC for Medical Devices (Annex II), on 12 January

2011; for a five-year term with an expiry date of 11 January 2016.

Intended Use, Indications for Use and Claims

The clinical and technical literature search for InvivoDental/TxStudio software focused on evaluating

the design, operation, performance and safety related to its intended or indications for use (below).

“InvivoDental is intended for use as a front-end software interface for the transfer of imaging

information from a medical scanner such as a Dental CT scanner. It is also intended for use as a

planning and simulation software in the placement of dental implants, orthodontics and surgical

treatment.”

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Author Thomas Navarro, RAC

January 2013 Page 4 of 18

3. Clinical Evaluation

Based on risk level and product classification, clinical investigation trials in human subjects were not

required for InvivoDental/TxStudio software.

4. Context of Literature Review

Purpose of the Review

This literature review was conducted through a search of medical literature and materials available on

the internet (http://www.ncbi.nlm.nih.gov/pubmed). PubMed comprises more than 22 million citations

for biomedical literature from MEDLINE, life science journals, and online books.

This clinical evaluation report is to support the marketing of Anatomage, Inc. InVivoDental/TxStudio

software. The purpose of this review is to find literature that addresses the safety and performance of

the product and any adverse effects related to InvivoDental, or it’s claimed predicate software marketed

and sold worldwide, and related to its intended use. Available published literature regarding

performance and adverse effects will be analyzed to review the safety of the software.

Search Strategy

This literature search was performed according to MEDDEV 2.7.1, and at the level of information

required for the risk posed for a Class IIa software product.

Considerations were made to determine compliance with additional guidelines by both MHRA and

AMTAC for issues related to product equivalence in evaluating and compiling this report.

Clinical Evaluation:

Software used for the same clinical condition or purpose

Software used at the same site of the body

Software used in a similar population

Software used has similar relevant critical performance for specific intended use

Technical Evaluation:

Software used under similar conditions of use

Software used has similar specifications and properties

Software used of similar design

Software used similar deployment methods

Software used has similar principles of operation

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Author Thomas Navarro, RAC

January 2013 Page 5 of 18

Search Methods and Criteria:

Date of Search: August 1993 to January 2013

Search Database Source: http://www.ncbi.nlm.nih.gov/pubmed

Search Terms 1: dental implant AND CT AND software

Search Terms 2: dental implant AND CBCT

Search Terms 3: Anatomage, InvivoDental, TxStudio

Search Results

Forty-seven (47) articles (published from 1993 to 2012) were identified in this literature search.

As early as August 1993, M. Klein, et al. from the Department of Implant Dentistry at New York

University Dental School published one of the first relevant articles entitled “A computerized

tomography (CT) scan appliance for optimal presurgical and preprosthetic planning of the implant

patient”. This article described the technique for using CT (computerized axial tomography) scans,

with specially-designed software and an adjunct appliance, for accurate planning of dental implants and

implant-supported restorations.

As late as December 2012, A. Weissheimer, et al. from the Department of Orthodontics at Catholic

University of Rio Grande in Brazil, published an article entitled “Imaging software accuracy for 3-

dimensional analysis of the upper airway”. The aim of this study was to compare the precision and

accuracy of several imaging software programs for measuring upper airway volumes in cone-beam

computed tomography data, including InvivoDental.

All relevant articles are grouped into the following four categories as determined by the primary focus

of each article:

1. Peer-reviewed Articles related to Radiological Image Processing Systems

2. Case Studies related to Anatomage InvivoDental software

3. Editorials and Expert Opinions (sorted by author last name)

4. Other Relevant Articles of Interest (sorted by author last name)

Copies of listed citations are available upon request.

Several other articles were also identified; however rejected (and excluded from this literature

evaluation report) for the following reasons:

Not relevant to the intended or indications for use of InvivoDental/TxStudio software.

Publications were not in a peer-reviewed journal (except for those related to problems)

Publications were in a foreign language (non-English)

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5. Data Appraisal

Review of Relevant Published Literature

Primary evidence of product safety and effectiveness is derived from published literature available to-

date, case studies with InvivoDental software, and FDA Manufacturer and User Facility Device

Experience (MAUDE) database (voluntary reports of adverse events involving medical devices).

The following peer-reviewed articles were deemed the most relevant to the clinical and technical

aspects of radiological image processing systems, including Anatomage InvivoDental software.

Peer-reviewed Articles related to Radiological Image Processing Systems

1. In October 1998, Kris Verstreken, Ph.D. and fellow associates from the Leuven University Hospital

in Gasthuisberg, Belgium published an article in the IEEE Transactions in Medical Imaging Journal

[17(5):842-52], entitled “An image-guided planning system for endosseous oral implants”. The

article described a preoperative planning system for oral implant surgery that was developed taking

inputted computed tomographies (CT's) of the jaws. The two-dimensional (2-D) re-slices of these

axial CT slices are computed and shown together with three-dimensional (3-D) surface rendered

models of the bone and computer-aided design (CAD)-like implant models. The technique was

developed for scanning and visualizing an eventual removable prosthesis together with the bone

structures. The evaluation of the planning done with the system showed the difference between 2-D

and 3-D planning methods. The validation studies measured the benefits of the 3-D approach

comparing plans made in 2-D mode. The benefits of a 3-D approach are evident where a prosthesis

is involved in the planning. For the majority of the patients, clinically important adjustments and

optimizations to the 2-D plans are made once the 3-D visualization is enabled, effectively resulting

in a better plan. The alterations so obvious that the 3-D plan stands out clearly, and the

improvements often avoid complications such as mandibular nerve damage, sinus perforations, etc.

2. In June 2008, Dr. Scott D. Ganz published an article in the Compendium of Continuing Education

for Dentistry [29(5):256-8, 260-2, 264-7], entitled “Defining new paradigms for assessment of

implant receptor sites: The use of computed tomography, cone-beam computed tomography

(CT/CBCT) and interactive virtual treatment planning for congenitally missing lateral incisors”.

This abstract cited an emerging technology that encompassed the first-generation CT/CBCT, and

interactive software applications that have slowly progressed and evolved into necessary tools for

diagnosis, treatment planning, and delivery of dental implant and associated restorative and surgical

procedures. The integration of these innovative tools has helped define new methods for

appreciating anatomy, improving accuracy, and enhancing pre-surgical prosthetic planning to

achieve true restorative-driven implant dentistry. The article also demonstrated how computed

tomography combined with interactive virtual treatment-planning software applications empowered

clinicians with enhanced diagnostic capabilities for implant receptor-site assessment, generating

new paradigms that eventually superseded older methods of pre-surgical planning for dental

implant reconstruction.

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3. In October 2008, Dr. Rubio-Serrano, et al. from the Valencia University Medical and Dental School

in Spain, published an article in Medicina Oral Patologia Oral y Cirugia Bucal [13(10):E661-5],

entitled “Software applied to oral implantology: update”. The citation indicated that software was

increasingly used for diagnosis, planning and treatment in oral implantology. Computer-aided

surgery allowed a greater accuracy in implant positioning, taking advantage of the amount of bone

available and facilitating minimally-invasive surgery. A CT with a radiographic template positioned

in the mouth is made for the patient; the data is stored on a CD in DICOM 3 format, and then

introduced in the computer where implant treatment will be planned. Program navigation improves

surgical accuracy through the aid of software-based images captured from CT or MRI and a

surgical instrument tracking system. Information is then collected by special-purpose cameras,

allowing the procedure to be viewed in real-time on a monitor. It proved useful in situations where

an exact implantation is demanded, such as anatomical limitations, space, atrophic maxillae, etc.

Articles reviewed agree in emphasizing the reliability and accuracy of the planning and computer-

assisted navigation systems available on the market at that time.

4. Also in 2008, Drs. Sakineh Nikzad and A. Azari from the Tehran Faculty of Dentistry in Iran

published an article in the International Journal of Medical Robotics [4(4):348-54], entitled

“Computer-assisted implant surgery with 1 year follow-up”. This article suggested that for success

with immediate loaded dental implants it is necessary that, prior to their placement, bone quantity

and quality as well as the biomechanical environment in which the implants are to function be

evaluated. However, conventional techniques then used for immediate implant placement lacked

sufficient precision and were usually accomplished by opening flap procedures. The purpose of this

paper was to report the benefit of sophisticated pre-operative diagnostic implant planning and a

flapless surgical approach with immediate loading. The report described the use of computed

tomography (CT) for three-dimensional (3D) evaluations of bone implant sites, an interactive

software program for 3D planning and the fabrication of stereo-lithographic models as custom

surgical templates. The degree of patient satisfaction was evaluated by periodic recall and by

adopting a specially designed analogue scale in each visit. The results netted the mean amount of

bone loss around the implants was 0.5 +/- 0.1 mm and the satisfactoriness scale was rated high (i.e.

81), at the end of 1 year. In conclusion, the use of stereo-lithographic appliances in accordance with

flapless surgery made immediate placement of the implants more predictable.

5. In early 2009, Valente F, et al. published an article in the International Journal of Oral and

Maxillofacial Implants [24(2):234-42], entitled “Accuracy of computer-aided oral implant surgery:

a clinical and radiographic study”. The purpose of the study was to evaluate the in vivo accuracy

of computer-aided, template-guided oral implant surgery by comparing the three-dimensional

positions of planned and placed implants, and its advantages over the traditional approach. Oral

implant therapy was performed in two treatment centers on eligible patients using computerized

tomography (CT)-based software planning and computer-aided design/computer-assisted

manufacture stereo-lithographic templates. A second CT scan was obtained after surgery.

Preoperative and postoperative CT images were compared (planned versus actual implant

positions), and the accuracy of this type of image-guided therapy was assessed. Twenty-five adult

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patients were included in this retrospective study; 17 were treated in center 1, and eight in center 2.

Of the 104 implants inserted with the computer-aided method, 100 integrated, giving a cumulative

survival rate of 96% (mean follow-up, 36 months). There were no major surgical complications.

With regard to accuracy, 89 implants were available for comparison. There was a statistically

significant correlation in the accuracy of any implants placed with the same guide. There was no

difference in accuracy data from the two private centers; nor could a learning curve be

demonstrated. Based upon this clinical study, the following observations were made: (1) computer-

aided oral implant surgery used in two treatment centers provided a higher likelihood (96%) of

implant survival, and (2) deviations from planned implant positions existed in the coronal and

apical portions of the implants as well as with implant angulation.

6. In September 2009, Katsoulis J, et al. published an article in Clinical Implant Dentistry and Related

Research [11(3):238-45], entitled “Prosthetically driven, computer-guided implant planning for the

edentulous maxilla: a model study”. The objective was to analyze computer-assisted diagnostics

and virtual implant planning and to evaluate the indication for template-guided flapless surgery and

immediate loading in the rehabilitation of the edentulous maxilla. Forty (40) patients with an

edentulous maxilla were selected for this study. The three-dimensional analysis and virtual implant

planning was performed with the NobelGuide software program (Nobel Biocare, Göteborg,

Sweden). Prior to the computer tomography aesthetics and functional aspects were checked

clinically. Either a well-fitting denture or an optimized prosthetic setup was used and then

converted to a radiographic template. This allowed for a computer-guided analysis of the jaw

together with the prosthesis. Accordingly, the best implant position was determined in relation to

the bone structure and prospective tooth position. For all jaws, the hypothetical indication for (1)

four implants with a bar overdenture and (2) six implants with a simple fixed prosthesis were

planned. The planning of the optimized implant position was then analyzed as follows: the number

of implants was calculated that could be placed in sufficient quantity of bone. Additional surgical

procedures (guided bone regeneration, sinus floor elevation) that would be necessary due the

reduced bone quality and quantity were identified. The indication of template-guided, flapless

surgery or an immediate loaded protocol was evaluated. The results: Model (a) - bar overdentures:

for 28 patients (70%), all four implants could be placed in sufficient bone (total 112 implants).

Thus, a full, flapless procedure could be suggested. For six patients (15%), sufficient bone was not

available for any of their planned implants. The remaining six patients had exhibited a combination

of sufficient or insufficient bone. Model (b) - simple fixed prosthesis: for 12 patients (30%), all six

implants could be placed in sufficient bone (total 72 implants). Thus, a full, flapless procedure

could be suggested. For seven patients (17%), sufficient bone was not available for any of their

planned implants. The remaining 21 patients had exhibited a combination of sufficient or

insufficient bone. In the maxilla, advanced atrophy is often observed, and implant placement

becomes difficult or impossible. Thus, flapless surgery or an immediate loading protocol can be

performed just in a selected number of patients. Nevertheless, the use of a computer program for

prosthetically driven implant planning is highly efficient and safe. The three-dimensional view of

the maxilla allows the determination of the best implant position, the optimization of the implant

axis, and the definition of the best surgical and prosthetic solution for the patient. Thus, a protocol

that combines a computer-guided technique with conventional surgical procedures becomes a

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promising option, which (the article concludes) needs to be further evaluated and improved.

7. In October 2009, Horwitz J, et al. published an article in Clinical Oral Implants Research

[20(10):1156-62], entitled “Accuracy of a computerized tomography-guided template-assisted

implant placement system: an in vitro study”. The objective was to evaluate the accuracy of

computer-assisted 3D planning and implant insertion using computerized tomography (CT). In the

study, nine implants were planned on pre-operative CTs of six resin models, which were acquired

with radiographic templates, using planning software (E implants). Each resin model contained

three pre-existing control implants (C implants). Radiographic templates were converted into

operative guides containing 4.8-mm-diameter titanium sleeves. A single set of insertable sleeves

was used for consecutively drilling the six models, followed by implant insertion through the guide

sleeves. Models were further divided into group A (the first three models) and group B (the last

three models). Post-operative CTs were used to compare implant positions with pre-operative

planned positions. Statistical analysis included the Mann-Whitney U test for E and C implants and

the Wilcoxon's signed ranks test for both groups. The results netted a mean apex depth deviations

for E and C implants [0.49 mm+/-0.36 standard deviation (SD) and 0.32 mm+/-0.21 SD,

respectively], and the mean apex radial deviations (0.63 mm+/-0.38 SD and 0.49 mm+/-0.17 SD,

respectively) were similar (P>0.05). The mean angulation deviations for E and C implants were

2.17+/-1.06 degrees SD and 1.33+/-0.69 degrees SD, P<0.05. E implant deviations of all the

parameters in group A were significantly smaller than E implant deviations in group B. In

conclusion, computer-assisted implant planning and insertion provided good accuracy. Deviations

are mainly related to system and reproducibility errors. Multiple uses of drills and titanium sleeves

significantly reduced system accuracy.

8. In November 2009, Dreiseidler T, et al. from the Department for Craniomaxillofacial and Plastic

Surgery at University of Cologne in Germany published an article in Clinical Oral Implants

Research [20(11):1191-9], entitled “Accuracy of a newly developed integrated system for dental

implant planning”. The objective was to evaluate the accuracy of the first integrated system for

cone-beam CT (CBCT) imaging, dental implant planning and surgical template-aided implant

placement. On the basis of CBCT scans, a total of 54 implant positions were planned for 10

partially edentulous anatomical patient-equivalent models. Surgical guides were ordered from the

manufacturer (SICAT). Two different types of guidance were assessed: for assessment of the

SICAT system inherent accuracy vendor's titanium sleeves of 2 mm internal diameter and 5 mm

length were utilized for pilot drills. The guide sleeves of the NobelGuide system were implemented

for fully guided surgery and implant insertion. Deviations perpendicular to the implant axes at the

crestal and apical end, as well as the angle deviations between the virtual planning data and the

surgical results, were measured utilizing a follow-up CBCT investigation and referential marker-

based registration. The SICAT system inherent mean deviation rates for the drilled pilot

osteotomies were determined to be smaller than 500 mum even at the apical end. Mean angle

deviations of 1.18 degrees were determined. Utilizing the NobelGuide sleeve-in-sleeve system for

fully guided implant insertion in combination with the investigated template technology enabled to

insert dental implants with the same accuracy. Crestal deviations, in general, were significantly

lower than the apical deviations. In conclusion: although hardly comparable due to different study

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designs and measurement strategies, the investigated SICAT system's inherent accuracy

corresponds to the most favorable results for computer-aided surgery systems published. In

combination with the NobelGuide surgical set for fully guided insertion, the same accuracy level

could be maintained for implant positioning.

9. In January 2010, Chiarelli T, et al. published an article in the International Journal of Computer

Assisted Radiology and Surgery [5(1):57-67], entitled “A fully 3D work context for oral implant

planning and simulation”. The purpose of most software systems for oral implantology are based

on a two-dimensional multi-view approach, often accompanied with a surface rendered model.

Usually they are affected by common errors like anisotropy of the volume and distortion on

measurements. A more integrated and realistic 3D approach for implant surgery was desirable in

order to gain a deeper and surer knowledge of patient's anatomy before inserting the implants, thus

reducing the risk of damaging surrounding structures. The methods presented a 3D software system

for oral implant planning where computer graphic techniques have been used to create a smooth

and user-friendly fully integrated 3D environment to work in. Both volume isotropy and

correctness in measurements are obtained through slices interpolation to achieve, respectively, an

isotropic voxel and the freedom of choosing arbitrarily, during the planning, the best cross-sectional

plane. Correct orientation of the planned implants is also easily computed, by exploiting a

radiological mask with radio-opaque markers, worn by the patient during the CT scan. Precision in

measures were validated by considering several different scans and comparing the measures

achieved with the ones got through the common methodology. It has been also calculated error

percentages, algorithms efficiencies, and performances. Precision achieved outperforms usual

DentaScan multi-view approach one, and it was comparable with or better than that obtained by the

DentalVox tool (from 0.16 to 0.71% error in measures). In conclusion, the proposed software

system provides a user-friendly, correct and precise work context for oral implant planning,

avoiding similar software common errors. The 3D environment can be also exploited in the final

surgical phase, in order to provide a flapless surgical guide, through the use of an anthropomorphic

robot.

Case Studies related to Anatomage Invivo Dental software

10. In July 2010, Dr. TS Kim, et al. published an article in the Journal of Endodontics [36(7):1191-4],

entitled “A comparison of cone-beam computed tomography and direct measurement in the

examination of the mandibular canal and adjacent structures”. The purpose of this investigation

was to assess the ability of cone-beam computed tomography (CBCT) scanning to measure

distances from the apices of selected posterior teeth to the mandibular canal. Measurements were

taken from the apices of all posterior teeth that were superior to the mandibular canal. A pilot study

was performed to determine the scanning parameters that produced the most diagnostic image and

the best dissection technique. Twelve (12) human hemimandibles with posterior teeth were scanned

at .20 voxels on an I-CAT Classic CBCT device (Imaging Sciences International, Hatfield, PA), and

the scans were exported in DICOM format. The scans were examined in InVivo Dental software

(Anatomage, San Jose, CA), and measurements were taken from the apex of each root along its

long axis to the upper portion of the mandibular canal. The specimens were dissected under a dental

operating microscope, and analogous direct measurements were taken with a Boley gauge. All

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measurements were taken in triplicate at least 1 week apart by one individual. The results were

averaged and the data separated into matching pairs for statistical analysis. The results were of no

statistical difference (alpha = .05) between the methods of measurement according to the Wilcoxon

matched pairs test (p = 0.676). For the anatomic measurements, the intra-rater correlation

coefficient (ICC) was .980 and for the CBCT it was .949, indicating that both methods were highly

reproducible. Both measurement methods were highly predictive of and highly correlated to each

other according to regression and correlation analysis, respectively. Based on the results of this

study, the I-CAT Classic can be used to measure distances from the apices of the posterior teeth to

the mandibular canal as accurately as direct anatomic dissection.

11. In January 2011, Bouwens DG, et al. published an article in the American Journal of Orthodontics

and Dentofacial Orthopedics [139(1):126-32], entitled “Comparison of mesiodistal root angulation

with post treatment panoramic radiographs and cone-beam computed tomography”. By way of

introduction, orthodontists assess mesiodistal root angulations before, during, and after orthodontic

treatment as an aid in establishing proper root position. Panoramic imaging has been useful for this

purpose and is a valuable screening tool in diagnosis and planning treatment of orthodontic

patients. Cone-beam computed tomography (CBCT) for imaging of the craniofacial complex

creates the opportunity to evaluate 3-dimensional images compared with traditional 2-dimensional

images. The purpose of this project was to compare mesiodistal root angulations by using post

treatment panoramic radiographic images and CBCT scans. Mesiodistal root angulations from

panoramic images and CBCT scans of 35 orthognathic surgery patients after orthodontic treatment

were compared. The panoramic images were measured by using VixWin (Gendex Dental Systems,

Des Plaines, Ill), and the CBCT scans by using InvivoDental 3D (Anatomage, San Jose, Calif). The

mesiodistal root angulation of each maxillary and mandibular tooth was measured by using the

occlusal plane as the reference line. With an intercept-only linear regression for correlated data

(with an unstructured covariance structure), the global test of whether the mean vector of all

differences for the teeth is zero was performed separately for the 2 arches. As a result, the global

test for both arches was statistically significant (P <0.001), indicating an overall difference in root

angulation between measurements from panoramic and CBCT images. There was no discernible

pattern in the average differences between panoramic and CBCT measurements. In conclusion, the

assessment of mesiodistal tooth angulation with panoramic radiography should be approached with

caution and reinforced by a thorough clinical examination of the dentition.

12. Dated Aug 2011, Nguyen E, et al. published an article in the American Journal of Orthodontics and

Dentofacial Orthopedics [140(2):e59-66], entitled “Accuracy of cone-beam computed tomography

in predicting the diameter of unerupted teeth”. As an introduction, an accurate prediction of the

mesiodistal diameter (MDD) of the erupting permanent teeth is essential in orthodontic diagnosis

and treatment planning during the mixed dentition period. The objective was to test the accuracy

and reproducibility of cone-beam computed tomography (CBCT) in predicting the MDD of

unerupted teeth. The secondary objective was to determine the accuracy and reproducibility of 3

viewing methods by using 2 CBCT software programs, InVivoDental (Anatomage, San Jose, Calif)

and CBWorks (CyberMed, Seoul, Korea) in measuring the MDD of teeth in models simulating

unerupted teeth. CBCT data were collected on the CB MercuRay (Hitachi Medical Corporation,

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Tokyo, Japan). Models of unerupted teeth (n = 25), created by embedding 25 tooth samples into a

polydimethylsiloxane polymer with a similar density to tissues surrounding teeth, were scanned and

measured by 2 investigators. Repeated MDD measurements of each sample were made by using 3

CBCT viewing methods: InVivo Section, InVivo Volume Render (both Anatomage), and CBWorks

Volume Render (CyberMed). These measurements were then compared with the MDD physically

measured by digital calipers before the teeth were embedded and scanned. As a result, all 3 of the

new methods had mean measurements that were statistically significantly less (P <0.0001) than the

physical method, adjusting for investigator and tooth effects. Specifically, InVivo Section

measurements were 0.3 mm (95% CI, -0.4 to -0.2) less than the measurements with calipers, InVivo

Volume Render measurements were 0.5 mm less (95% CI, -0.6 to -0.4) than those with calipers,

and CBWorks Volume Render measurements were 0.4 mm less (95% CI, -0.4 to -0.3) than those

with calipers. Overall, there were high correlation values among the 3 viewing methods, indicating

that CBCT can be used to measure the MDD of unerupted teeth. The InVivo Section method had

the greatest correlation with the calipers.

13. In August 2012, Lee H, et al. published an article in the American Journal of Orthodontics and

Dentofacial Orthopedics [142(2):179-85], entitled “Mandibular dimensions of subjects with

asymmetric skeletal class III malocclusion and normal occlusion compared with cone-beam

computed tomography”. The purpose of this study was to use cone-beam computed tomography to

compare mandibular dimensions in subjects with asymmetric skeletal Class III malocclusion and

those with normal occlusion. The methods used were cone-beam computed tomography scans of 38

subjects with normal occlusion and 28 patients with facial asymmetry were evaluated and digitized

with Invivo software (Anatomage, San Jose, Calif). Three midsagittal and 13 right and left

measurements were taken. The paired t test was used to compare the right and left sides in each

group. The Mann-Whitney U test was used to compare the midsagittal variables and the differences

between the 2 sides of the group with normal occlusion with those of asymmetry patients. As a

result, the posterior part of the mandibular body showed significant differences between the

deviated and nondeviated sides in asymmetric Class III patients. The difference of the asymmetry

group was significantly greater than that of the normal occlusion group for the mediolateral ramal

and the anteroposterior condylar inclinations (P = 0.007 and P = 0.019, respectively). In conclusion,

the asymmetric skeletal Class III group showed significant differences in condylar height, ramus

height, and posterior part of the mandibular body compared with the subjects with normal

occlusion. These results might be useful for diagnosis and treatment planning of asymmetric Class

III patients.

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14. In August 2012, Ryu JH, et al. published an article in the American Journal of Orthodontics and

Dentofacial Orthopedics [142(2):207-12], entitled “Palatal bone thickness compared with cone-

beam computed tomography in adolescents and adults for mini-implant placement”. The purpose of

this study was to compare the bone thickness of the palatal areas in early and late mixed and early

permanent dentitions according to dental age. Cone-beam computed tomography scans of 118

subjects were selected and divided into 38 early mixed (8.03 ± 0.93 years), 40 late mixed (11.51 ±

0.92 years), and 40 permanent (20.92 ± 1.17 years) dentition subjects. The measurements of palatal

bone thickness were made at 49 sites by using InVivoDental software (Anatomage, San Jose,

Calif). Repeated measures analysis of variance was used to analyze intragroup and intergroup

differences as well as sex dimorphism. The results were significantly lower bone thickness in the

early mixed dentition group than in the 2 other groups (P <0.001). Bone thickness was higher in the

anterior region than in the middle and posterior regions (P <0.001). Also, significant differences

were found among the midline, medial, and lateral areas of the palate. In conclusion, palatal bone

thicknesses were significantly lower in the early mixed dentition group than in both the late mixed

and permanent dentition groups. These findings might be helpful for clinicians to enhance the

successful use of temporary anchorage devices in the palate.

15. In December 2012, Weissheimer A, et al. published an article in the American Journal of

Orthodontics and Dentofacial Orthopedics [142(6):801-13], entitled “Imaging software accuracy

for 3-dimensional analysis of the upper airway”. The aim of this study was to compare the

precision and accuracy of 6 imaging software programs for measuring upper airway volumes in

cone-beam computed tomography data. The sample consisted of 33 growing patients and an

oropharynx acrylic phantom, scanned with an i-CAT scanner (Imaging Sciences International,

Hatfield, Pa). The known oropharynx acrylic phantom volume was used as the gold standard. Semi-

automatic segmentations with interactive and fixed threshold protocols of the patients' oropharynx

and oropharynx acrylic phantom were performed by using Mimics (Materialise, Leuven, Belgium),

ITK-Snap (www.itksnap.org), OsiriX (Pixmeo, Geneva, Switzerland), Dolphin3D (Dolphin

Imaging & Management Solutions, Chatsworth, Calif), InVivoDental (Anatomage, San Jose, Calif),

and Ondemand3D (CyberMed, Seoul, Korea) software programs. The intraclass correlation

coefficient was used for the reliability tests. A repeated measurements analysis of variance

(ANOVA) test and post-hoc tests (Bonferroni) were used to compare the software programs. As a

result, the reliability was high for all programs. With the interactive threshold protocol, the

oropharynx acrylic phantom segmentations with Mimics, Dolphin3D, OsiriX, and ITK-Snap

showed less than 2% errors in volumes compared with the gold standard. Ondemand3D and InVivo

Dental had more than 5% errors compared with the gold standard. With the fixed threshold

protocol, the volume errors were similar (-11.1% to -11.7%) among the programs. In the

oropharynx segmentation with the interactive protocol, ITK-Snap, Mimics, OsiriX, and Dolphin3D

were statistically significantly different (P <0.05) from InVivo Dental. No statistical difference

(P >0.05) was found between InVivo Dental and OnDemand3D. In conclusion, all 6 imaging

software programs were reliable but had errors in the volume segmentations of the oropharynx.

Mimics, Dolphin3D, ITK-Snap, and OsiriX were similar and more accurate than InVivo Dental and

Ondemand3D for upper airway assessment.

ANATOMAGE CR001 01/24/13 Rev. B

Clinical Evaluation Report: Literature Review

Author Thomas Navarro, RAC

January 2013 Page 14 of 18

Editorials and Expert Opinions

16. Chenin DL. 3D cephalometrics: the new norm. Alpha Omegan. 2010 Jun; 103(2):51-6.

17. Chiarelli T, Lamma E, Sansoni T. A fully 3D work context for oral implant planning and simulation.

Int J Comput Assist Radiol Surg. 2010 Jan; 5(1):57-67. Epub 2009 Jul 24.

18. Horwitz J, Zuabi O, Machtei EE. Accuracy of a computerized tomography-guided template-assisted

implant placement system: an in vitro study. Clin Oral Implants Res. 2009 Oct; 20(10):1156-62.

Epub 2009 Jun 10.

19. Katsoulis J, Pazera P, Mericske-Stern R. Prosthetically driven, computer-guided implant planning

for the edentulous maxilla: a model study. Clin Implant Dent Relat Res. 2009 Sep; 11(3):238-45.

Epub 2008 Sep 9.

20. Lai RF, Zou H, Kong WD, Lin W. Applied anatomic site study of palatal anchorage implants using

cone beam computed tomography. Int J Oral Sci. 2010 Jun; 2(2):98-104.

21. Nikzad S, Azari A. Computer-assisted implant surgery; a flapless surgical/immediate loaded

approach with 1 year follow-up. Int J Med Robot. 2008 Dec; 4(4):348-54.

22. Ozan O, et al. Clinical application of stereolithographic surgical guide with a handpiece guidance

apparatus: a case report. J Oral Implantol. 2012 Oct; 38(5):603-9. Epub 2011 Jul 18.

23. Patel N. Integrating three-dimensional digital technologies for comprehensive implant dentistry. J

Am Dent Assoc. 2010 Jun; 141 Suppl 2:20S-4S.

24. Rubio Serrano M, et al. Software applied to oral implantology: update. Med Oral Patol Oral Cir

Bucal. 2008 Oct 1; 13(10):E661-5.

25. Ruiz JL. An evidence-based concept of implant dentistry. Utilization of short and narrow platform

implants. Dent Today. 2012 Sep; 31(9):94, 96-9.

26. Wagner A, et al. Computer-aided placement of endosseous oral implants in patients after ablative

tumour surgery: assessment of accuracy. Clin Oral Implants Res. 2003 Jun; 14(3):340-8.

27. Valente F, Schiroli G, Sbrenna A. Accuracy of computer-aided oral implant surgery: a clinical and

radiographic study. Int J Oral Maxillofac Implants. 2009 Mar-Apr; 24(2):234-42.

28. Valiyaparambil JV, et al. Bone quality evaluation: comparison of cone beam computed tomography

and subjective surgical assessment. Int J Oral Maxillofac Implants. 2012 Sep; 27(5):1271-7.

29. Verstreken K, et al. An image-guided planning system for endosseous oral implants. IEEE Trans

Med Imaging. 1998 Oct; 17(5):842-52.

ANATOMAGE CR001 01/24/13 Rev. B

Clinical Evaluation Report: Literature Review

Author Thomas Navarro, RAC

January 2013 Page 15 of 18

Other Relevant Articles of Interest

30. Carrafiello G, et al. Comparative study of jaws with multislice computed tomography and cone-

beam computed tomography. Radiol Med. 2010 Jun; 115(4):600-11. Epub 2010 Feb 22.

31. Dreiseidler T, et al. Accuracy of a newly developed integrated system for dental implant planning.

Clin Oral Implants Res. 2009 Nov; 20(11):1191-9.

32. Ganz SD. Computer-aided design/computer-aided manufacturing applications using CT and cone

beam CT scanning technology. Dent Clin North Am. 2008 Oct; 52(4):777-808, vii.

33. Ganz SD. Defining new paradigms for assessment of implant receptor sites. The use of CT/CBCT

and interactive virtual treatment planning for congenitally missing lateral incisors. Compend

Contin Educ Dent. 2008 Jun; 29(5):256-8, 260-2, 264-7; quiz 268, 278.

34. Ganz SD. Techniques for the use of CT imaging for the fabrication of surgical guides. Atlas Oral

Maxillofac Surg Clin North Am. 2006 Mar; 14(1):75-97.

35. Hagiwara Y, Koizumi M, Igarashi T. Application of CT imaging for dental implant simulation. J

Oral Sci. 1999 Dec; 41(4):157-61.

36. Jang HY, et al. Choice of graft material in relation to maxillary sinus width in internal sinus floor

augmentation. J Oral Maxillofac Surg. 2010 Aug; 68(8):1859-68. Epub 2010 May 26.

37. Klein M, Cranin AN, Sirakian A. A computerized tomography (CT) scan appliance for optimal

presurgical and preprosthetic planning of the implant patient. Pract Periodontics Aesthet Dent.

1993 Aug; 5(6):33-9; quiz 39.

38. Mandelaris GA, et al. Computer-guided implant dentistry for precise implant placement: combining

specialized stereo lithographically generated drilling guides and surgical implant instrumentation.

Int J Periodontics Restorative Dent. 2010 Jun; 30(3):275-81.

39. Parel SM, Triplett RG. Interactive imaging for implant planning, placement, and prosthesis

construction. J Oral Maxillofac Surg. 2004 Sep; 62(9 Suppl 2):41-7.

40. Peck JN, Conte GJ. Radiologic techniques using CBCT and 3-D treatment planning for implant

placement. J Calif Dent Assoc. 2008 Apr; 36(4):287-90, 292-4, 296-7.

41. Pettersson A, et al. Accuracy of CAD/CAM-guided surgical template implant surgery on human

cadavers: Part I. J Prosthet Dent. 2010 Jun; 103(6):334-42.

42. Poeschl PW, et al. Comparison of cone-beam and conventional multislice computed tomography for

image-guided dental implant planning. Clin Oral Investig. 2013 Jan; 17(1):317-24.

ANATOMAGE CR001 01/24/13 Rev. B

Clinical Evaluation Report: Literature Review

Author Thomas Navarro, RAC

January 2013 Page 16 of 18

43. Spector L. Computer-aided dental implant planning. Dent Clin North Am. 2008 Oct; 52(4):761-75,

vi.

44. Stockham CD. Using CT and SIM/Plant to plan implant therapy. Alpha Omegan. 1996 Winter;

89(4):35-8.

45. Tipton WL, Metz P. Three dimensional computed technology--a new standard of care. Int J Orthod

Milwaukee. 2008 Spring; 19(1):15-21.

46. Vanderven FJ. CT scanning vs. panoramic radiography. A comparison of the diagnostic advantages

of panoramic radiography and computed tomography scanning for placement of root form dental

implants. J Colo Dent Assoc. 1995 Apr; 73(4):26-8, 30, 38.

47. Zheng G, et al. The implementation of an integrated computer-aided system for dental

implantology. Conf Proc IEEE Eng Med Biol Soc. 2008; 2008:58-61.

Evaluation of Adverse Reports from FDA MAUDE database

The FDA MAUDE database was researched under the product classification code “LLZ” for similar

devices as radiological image processing systems. Reported adverse events since 1993 were evaluated

to determine whether Anatomage adequately identified all associated risks with InVivoDental in its risk

management program.

There were ten (10) reported deaths in which a radiological image processing device may have

contributed to the outcome. While these devices have the same classification code as InvivoDental,

their function and intended use is very different. For instance, InvivoDental is not a system that shares

images across an enterprise network. In several cases, critical information was not accessible during

patient treatment; however, it was not concluded in these reports that the devices were a cause. The

remaining reported incidents were concluded to be the result of an operator error.

There were twenty-three (23) reported injuries reported in which a radiological image processing

device may have contributed to the outcome. Most of these devices are PACS systems that are used to

distribute images over a network and are dissimilar to InVivoDental in their intended use; because of

this the probability, these adverse event resulting in an injury from the intended use of InVivoDental

are greatly reduced. For example, data loss from a capture device made it necessary to expose the

patient to x-rays again. However, this type of malfunction is not possible with InVivoDental because

the software imports data that is already stored as DICOM files to construct volume images. Other

reported injuries were caused by human error, data loss, incorrect patient information, and system

failure.

ANATOMAGE CR001 01/24/13 Rev. B

Clinical Evaluation Report: Literature Review

Author Thomas Navarro, RAC

January 2013 Page 17 of 18

Malfunctions were also reported as adverse events for radiological image processing devices. The

majority of malfunctions are attributed to human error where the device was working properly and

system “crashes” which may have rendered the device temporarily unusable. No malfunctions were

reported as adverse events for Anatomage or InvivoDental software on the FDA MAUDE database.

The hazards identified and their associated failure modes accurately represent recorded experiences

where similar devices reported incidents of death, injury, and malfunction. The hazards associated with

these types of adverse events have been considered in Anatomage risk analysis and documented steps

have been taken to mitigate these hazards.

6. Data Analysis

Performance

Literature reviews do not report any performance issues associated with dental implant planning

software. There are no reported features that are missing or insufficient. Indeed, much of the literature

supports the advantages of using software for implant planning.

Safety

A review of the literature also revealed no reported complications arising from use of dental implant

planning software. In addition there are no reports of limitations of the intended use or misuse of the

software for other than its intended purpose. Rather it is recognized that dental implant planning and

placement is a complex task. Dental implant planning software enables clinicians to better plan and

place implants. The literature is abundant in conclusions that advanced imaging and software offer

advances in dental implant planning and placement.

7. Conclusions

InVivoDental software is found to be in compliance with the essential requirements.

Safety and effectiveness claims found in the Instructions for Use are supported by this clinical

evaluation report.

Risk control for InVivoDental software is adequate and its design, verification, and validation measures

are effective.

ANATOMAGE CR001 01/24/13 Rev. B

Clinical Evaluation Report: Literature Review

Author Thomas Navarro, RAC

January 2013 Page 18 of 18

Revision Summary of Changes Date

A Initial Release 07/02/2010

B This update expanded the inclusive date(s) of search to encompass

earlier citations for data appraisal retroactive from 1993 to-date; listed

newer citations from 2010 to-date; and omitted all irrelevant items. The

peer-reviewed articles were then categorized according to product type,

related case studies, editorials/expert opinions, and other relevant

articles. An FDA MAUDE database search was also completed and

reported adverse events were evaluated to the Anatomage risk

management program.

01/24/2013