Summary of Safety and Effectiveness Data

I. General Information

#### Device Generic Name Digital Mammographic X-ray System

**[Device Trade Name]{.underline}** SenoScan^^ Full Field Digital
Mammography System

**[Applicant's Name and Address]{.underline}** Fischer Imaging
Corporation

12300 North Grant St.

Denver, CO 80026

**[PMA Number:]{.underline}** P010017

**[Date of Good Manufacturing Practices Inspection:]{.underline}**
September 20, 2001

**[Date of Notice of Approval to the Applicant:]{.underline}** September
25, 2001

# II. Indications for use

The SenoScan^®^ Full-Field Digital Mammography System is a dedicated
mammography system intended to produce radiographic images of the human
breast for the purpose of diagnostic and screening mammography. The
SenoScan^®^ Full-Field Digital Mammography system is intended to be used
in the same clinical applications as traditional film-based mammographic
systems.

III\. Device Description

The SenoScan^®^ Full-Field Digital Mammography System (SenoScan^®^)
includes a digital image receptor combined with a conventional
mammographic X-ray device except for the collimator. The system consists
of a dual filament x-ray tube, slit-collimator, x-ray generator, support
arm, support assembly, compression device and CCD digital detector with
readout equipment. The arm assembly consists of an X-ray tube on one end
and a digital detector on the other end. The entire arm assembly pivots
at the focal spot of the x-ray tube as the detector scans from left to
right. The slit-collimator shapes the beam and limits the x-ray beam to
the 1-cm active width of the detector. This results in images with very
little scatter and no dose penalty associated with absorption of primary
radiation by a grid.

The detector consists of an array of 4 charge-coupled devices (CCD). The
CCDs have a sensitive element matrix of 405 x 2048 pixels. A cesium
iodide (CsI) scintillator doped with thallium is chosen for its high
detective quantum efficiency and its rapid decay time (less than 3 μs).
The overall detector size is approximately 1 cm x 22 cm. It is scanned
over 30 cm, resulting in a 22 cm x 30-cm image.

The SenoScan^®^ also includes an Acquisition Station and Review Station
directly connected via Ethernet or Fiber Distributed Data Interface
(FDDI). The Acquisition Station resides at the gantry for the purpose of
image acquisition and quality control. Once accepted by the
technologist, the image is sent to the Review Station. The softcopy
image can then be reviewed on one or two 2K x 2.5K high-resolution
monitors. The images are stored on a RAID array (redundant array of
independent drives) which has a capacity from 45 gigabytes to 1.2
terabytes. Images can be printed on a laser printer using Dicom Print
Services. Images can be archived either to a PACS using DICOM 3.0 or to
a magneto-optical disk drive for long-term storage.

The following components are certified for use with SenoScan^®^.
Certification is applicable when components are installed, calibrated,
and serviced in accor­dance with all applicable instructions.
Unauthorized modifications will invalidate certification.

> *•* SenoScan^®^ Gantry 94500G-2
>
> • X-ray Tube 94518-2
>
> • Collimator/Filter Assembly 947 LOM-2
>
> • Detector 94767-1
>
> *•* SenoScan^®^ Generator 94100G-2
>
> • HF/HV Transformer Assembly 94060M-2
>
> • Inverter Assembly 94030M-2
>
> *•* SenoScan^®^ Acquisition Station 94830G-1

• SenoScan^®^ Acquisition Station Computer 94502-1

The following laser film imaging systems have been qualified for use
with SenoScan^®^. These hard copy film printers have been tested and
found to be fully compatible with the SenoScan^®^ system when installed,
maintained, and operated in accordance with the manufacturer's
instructions.

> • Kodak Dry View 8610 Laser Imaging System/for Mammography
>
> • Agfa Scopix LR 5200 Laser Irnager

**Note: Although** a **printer** is **listed as an option, facilities
must have the ability to transfer usable images to other facilities and
to patients. At this time, the indicated laser imagers are the only
devices qualified for this task.**

# IV. Contraindications

None known.

# 

# V. Warnings and Precautions

-   This equipment is not suitable for use in the presence of a
    flammable anesthetic mixture with air or oxygen or nitrous oxide.

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-   Operators should remain behind the provided lead-glass shielding
    during an x-ray exposure. To prevent exposure to x-ray, the operator
    must remain behind the technologist shield, in the zone of occupancy
    shown at the left, during the entire exposure.

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-   For U.S. only, until further direction is available from the FDA,
    the SenoScan^®^ Full Field Digital Mammography System must only be
    used in MQSA screen-film accredited/certified facilities.

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-   The acquisition workstation should not be used for final
    interpretation of patient studies.

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-   For compatible Laser printers, see the Qualified Components listing
    in this section of the manual and the latest product data sheets.
    These sheets are available from your local sales representative.

-   Operators should be trained to properly operate the user interface
    and review workstation. Only authorized trained personnel may
    operate this equipment. It is the responsibility of the site to
    ensure that proper operating techniques and procedures are followed
    when using mammographic x-ray equipment.

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-   Operators must ensure maximum radiological protection is provided to
    all persons present during x-ray operations. No
    unauthorized/unprotected person should be allowed in the room during
    x-ray operation.

-   Quality control procedures must be followed to ensure continued high
    level of operation and be in compliance the MQSA regulations.

-   Compression paddles must be carefully handled to prevent damage.
    Before use, compression paddles must be examined for the presence of
    cracks, sharp edges, roughness, and foreign matter, which may cause
    discomfort or injury to the patient. When not in use, compression
    paddles should be carefully stored in a manner that protects the
    paddles from damage.

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-   The provided on-screen ruler tool assumes that all measurements are
    made on a virtual surface located 2 cm above the breast support.
    Therefore, objects in the image which are above the virtual plane
    may be slightly larger than measured and those below the plane may
    be slightly smaller than measured.

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-   The review station should be located in a suitably dark environment
    to enhance image visibility during review. The ambient light level,
    measured at the surface of the monitor screen (with the monitor
    turned off), must not exceed 50 lux.

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-   This system contains no user serviceable parts. DO NOT remove any
    covers.

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-   Covers should be removed by qualified service personnel only.
    Installation and service should be performed only by qualified
    service personnel. Installation and Service manuals are available
    and should be consulted.

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-   Avoid touching the recording surface of any magnetic or optical
    storage media. Store recording media in approved manner and do not
    leave recording media exposed to any potentially harmful
    environments. Before usage, verify that there are no noticeable
    scratches or other imperfections that could potentially affect
    performance of the media.

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-   Unauthorized (third-party) software should not be added to the
    acquisition or review station computers. Addition of unauthorized
    software has the potential of affecting system performance or
    causing conflicts with system operation.

-   DO NOT attempt to operate a system that has not been properly
    installed. The gantry, acquisition station/technologist shield, and
    generator must be properly anchored to the floor and all shielding
    and wiring must conform to the installation specifications.

-   DO NOT use any accessories or other items not specifically intended
    for use with this x-ray system. Adverse effects may occur from
    foreign materials located in the x-ray beam.

-   Before removing any component or assembly to be sent out for
    servicing:

1.  Determine if the component has been exposed to any body fluids. If
    so, wear proper personal protective equipment (gloves, gown, mask,
    goggles, etc.) when accomplishing steps 2 through 4.

2.  Clean and disinfect the component as described in the Cleaning and
    Disinfection section of this manual.

3.  Remove the component from the system and inspect any previously
    inaccessible surfaces for possible contamination. Clean and
    disinfect these surfaces as necessary

4.  Place the component in a standard Red Biohazard bag, bearing the
    proper biohazard symbols, and seal.

5.  Carefully package the component for shipping.

## VI. Potential Adverse Effects of the Device on Health

The following list of potential adverse events apply to mammography and
are also applicable to digital mammography using the SenoScan^®^. No
adverse events were observed during the clinical trials.

Excessive breast compression

Excessive X-ray exposure

Electric shock

Infection

Skin irritation, abrasion, or puncture wounds.

VII\. Alternative Practices and Procedures

There are several methods available for screening and diagnosing cancer
in the breast. These include clinical breast examination, screen-film
mammography, digital mammography, ultrasound examination and magnetic
resonance imaging. After an abnormality is determined, a biopsy may be
performed to diagnose the cancer.

VIII\. Marketing History

SenoScan^®^ has only been used in clinical trials. SenoScan^®^ has not
yet been made available for commercial distribution anywhere in the
world. The x-ray portion, excluding the collimator, has been used for
film-screen mammography for many years.

# IX. Summary of Nonclinical Studies

The x-ray portion of the equipment is comparable to that found in
traditional screen-film mammographic systems. A series of laboratory
studies were undertaken to evaluate the SenoScan**^®^** physics
performance with respect to the digital receptor and image display. The
following characteristics were investigated: x-ray beam quality;
detector sensitometric response, overall system resolution,
signal-to-noise ratio, detective quantum efficiency, and radiation dose
as mean glandular dose.

######### X-ray Beam Quality

A typical measurement of the beam half-value layer (HVL) as a function
of peak kilo-voltage (kVp) is presented in Figure 1. The SenoScan^®^
beam quality exceeds the FDA minimum at all relevant values for kVp.

![](media/image1.wmf)

**Figure 1. SenoScan^®^ incident x-ray beam quality as a function of
kVp. (Half**

**value layer, mm Aluminum, obtained with compression paddle in the
beam)**

[Detector Sensitometric Response]{.underline}

X-rays attenuated by the detector scintillator are converted into light
energy. The CCD transforms the light energy into an electric charge. The
electric charge forms an analog voltage that is then con­verted into
digital values by the data acquisition system. That sys­tem offers a
number of gain settings that provide various sensitomet­ric responses
(i.e. digital value vs. radiation exposure curve). Gain settings are
selected for optimal imaging characteristics and allow for optimal
exposure. The benefit of multiple gain settings can be seen particularly
in the high-resolution mode of operation. Figure 2 shows a typical
detector sensitometric response curve as a function of incident
exposure, in the Standard mode. The curves demonstrate linear response
over the system practical dynamic ranges.

![](media/image2.wmf)

> **Figure 2. Detector system sensitometric response in the Standard
> mode, 54-μm** **pixels, obtained after offset correction at 28 kVp,
> gain #1.**

Figure 3 presents the sensitometric response associated with gain number
3. Higher gain in this mode makes more efficient use of the available
quantum energy. In High-resolution mode, the pixel size is ¼ of the
available pixel area in the standard imaging mode.

![](media/image3.wmf)

Figure 3. Detector system sensitometric response with gain number 3,
obtained after offset correction, at 29 kVp. Gain 3 is used in
high-resolution mode.

> Finally, Figure 4 presents an image noise-variance versus expo­sure
> plot for gain #2 at 29 kVp. The linearity of the graph demon­strates
> that the SenoScan^®^ operates in a quantum-limited mode over a wide
> range of detector exposures, including exposures well below those
> expected in routine clinical imaging.

![](media/image4.wmf) **Figure 4. Image noise variance as a function of
detector exposure, gain #2, 29 kVp**

######### Detective Quantum Efficiency

The detective quantum efficiency (DQE) provides a quantitative measure
of the efficiency of SNR transfer of the image acquisition system. While
the radiologist is the ultimate judge of diagnostic content of medical
images, the detective quantum efficiency (DQE) is widely accepted as the
most relevant figure of merit to quantita­tively characterize the image
quality of medical x-ray systems. Medical imaging system performance can
often be evaluated in terms of detection performance characteristics.
The DQE character­izes a detection system, and can be interpreted as the
efficiency of such system in transmitting the information it receives.
Specifically, the DQE can be described as the fraction of incident
photons that would have to be detected without additional (detector)
noise to yield the same signal-to-noise (SNR) ratio as is actually
observed[^1]. Therefore, it is a measure of detection performance (SNR)
as a func­tion of frequency that accounts for dose. The noise factor
derived from the DQE, NF=l/(DQE)l/2 is the decrease in SNR that
accom­panies the detection process.

Accordingly, the DQE, defined as:

> *(SNR~out~(v)/SNR~in~ (v))^2^*

-   Includes combined effects of the modulation transfer function (MTF)
    and all relevant noise.

> **---** Remains stable under spatial filtering that affects the MTF.

-   Facilitates the comparison of different imaging systems.

The DQE as measured on an imaging system will always be less than the
DQE of the detector alone. Indeed, the system measure­ment necessarily
includes MTF reducing factors such as the finite focal spot aperture,
off-focal radiation, and other components such as grids that reduce
scattered radiation but require increased patient dose.

It should be noted that this evaluation was conducted using a com­plete
imaging system. Readers should use caution in comparing DQE
measurements. Other published DQE measurements may rep­resent 'detector
only' calculations. 'Detector only' calculations may not include
important contributing factors to resolution or dose deg­radation.
Further DQE exposure measurements obtained on a labo­ratory system
demonstrate DQE as a function of exposure.

> Sensitometry and Mean-Variance
>
> X-ray sensitometry was evaluated by performing a series of imaging
> exposures under a variety of conditions of kilovoltage (kV) and tube
> current settings. To extend the range of measurement, observations
> were also recorded with different thicknesses of poly-methyl
> meth­acrylate (PMMA) attenuating slabs placed in the beam. The expo­sure
> time was fixed by the scanning time of the system. A region of
> interest is selected in the image and the mean image digital signal
> pixel value (referred to hereafter as P) is recorded as well as the
> vari­ance of signal within the region. In addition, the tube current
> (mA) and the exposure in mR incident on the detector were recorded.
>
> The variance of the digital signal is also plotted vs the mean value
> to assess the contribution to the image noise from quantum and
> non­quantum sources and to estimate the dynamic range.
>
> X-ray Spectrum
>
> The purpose of this measurement is to estimate the shape of the
> spectrum so that the number of input quanta to the detector can be
> used in the calculation of DQE. A CdZnTe room temperature
> spec­trometer, with a 100 :m pinhole at its entrance, was located at a
> dis­tance of approximately 20 cm from the detector and aligned with the
> central ray of the x-ray beam. Spectra were measured to estimate the
> shape of the spectrum. At least 500 counts were acquired at the peak
> of the spectrum.
>
> Exposure was measured with a Keithley mammographic ionization chamber,
> corrected for temperature and pressure. The measured ex­posure was used
> to obtain an absolute calibration of the spectrum.
>
> MTF
>
> Modulation transfer function was evaluated by imaging a slanted edge
> composed of a sheet of niobium foil with ground edges mount­ed on a
> larger sheet of aluminum. This was placed at a location 4 cm from the
> detector. This provided a moderate contrast transition. The slanted
> edge \~1:16, provided approximately l0x oversampling.
>
> MTF was determined in both the direction along the slot detector and
> in the scanning direction at several kilovoltages. In addition, to
> assess possible hysteresis effects, MTF was measured in both the
> ris­ing and falling directions of signal.
>
> NPS
>
> The noise power spectra were measured from images of a uniformly
> attenuating PMMA phantom. After standard flat-fielding, the image is
> segmented into multiple sections, each of size 32x32 pixels. These are
> integrated in one dimension (x or y) to synthesize "slit" images. A
> standard, one-dimensional Fourier-transform based noise power spectrum
> is calculated in both x and y directions. The spectra from each region
> are then averaged to reduce the uncertainty in the final NPS. NPS data
> were acquired at four kilovoltages and at several in­tensity levels
> obtained by varying tube current (mA) and the thick­ness of PMMA
> attenuator in the x-ray beam.

## DQE

> The spatial frequency dependent DQE was calculated from the x-ray
> spectrum, MTF and NPS using the definition:
>
> P^2^ **·** MTF^2^ (f)
>
> DQE(f) = \-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\-\--
>
> (n/a) **·** NPS(f)
>
> where a is the area of the detector element, and n is the number of
> x­-ray quanta incident on the detector element. Therefore (n/a) is the
> entrance x-ray quantum fluence to the detector (obtained from the
> exposure and the spectral measurement).
>
> DQE(0) was estimated by extrapolating the mean of the DQE values in
> the slot and scan directions from the two lowest frequency points
> measured.

[DQE Performance Characterization]{.underline}

The smaller pixel size of the SenoScan^®^ system extends the effective
detection capability for this system well beyond a frequency of 5 cy­cles
per mm. Measurable DQE between *5* and 10 cycles per mm means that
SenoScan^®^ is capable of distinguishing much smaller ob­jects. Also, the
SenoScan^®^ system exhibited a zero spatial frequency DQE of 32% for 28
kVp. This is shown in Figure 5.

![](media/image6.wmf)

**Figure 5. SenoScan^®^ DQE at 28 kYp, 150 mA, and 4.2 cm PMMA in the
beam.**

These DQE data indicate clearly the detection efficiency achieved by a
combination of slot scanning (and associated scatter rejection) and
digital detector, over a range of frequencies that extend out through 10
LP/mm. The true system performance indicated by these measurements
should translate into improved conspicuity of minute lesions requiring
non-vanishing DQE at relatively high frequencies. Published DQE
measurements are often "detector only", that is do not include the
effect of a scatter-rejection grid. Generally speaking, DQE measurements
with a grid will be about 50% of those obtained without a grid, although
the actual variation will depend on the amount of scattered radiation
generated by the object being imaged and rejected by the grid. The
SenoScan^®^ System DQE measurement supports the claim that SenoScan^®^
could significantly reduce dose in a patient population.

Figure 6 presents system SenoScan^®^ DQE measurements as a func­tion of
detector exposure, for four different spatial frequencies.

![](media/image7.wmf)**Figure 6. DQE data for the SenoScan^®^ System as
a function of exposure.**

[Patient Radiation Dose Studies]{.underline}

Table 1 shows the calculated mean glandular dose for the produc­tion
SenoScan^®^ system based on the technique chart for a 50/50
adi­pose/fibroglandular breast composition. The technique chart is
de­rived by setting technique factors to achieve a constant ADU re­sponse.
A constant ADU response assures that the exposure is adequate across a
complete range of compressed thicknesses. The 4.2-cm SenoScan^®^ dose
was interpolated from the available data for direct comparison with the
data given in Tesic et al.[^2], Suleiman et al.[^3], and Rothenberg[^4].
Figure 7 presents the same information in a graphical form.

Table 1. Mean glandular dose for the recommended exposure techniques for
50/50 breast composition.

+---------+------+------+--------------+---------------+-------------+
| Breast  | kVp  | mA   | *SenoScan^®^ | FSM MGD,\     | \% decrease |
| thic    |      |      | MGD,\        | mRad          | in          |
| kness,\ |      |      | mRad*        |               |             |
| cm      |      |      |              |               | dose        |
+---------+------+------+--------------+---------------+-------------+
| 2       | 26   | 110  | 72           |               |             |
+---------+------+------+--------------+---------------+-------------+
| 3       | 27   | 140  | 80           |               |             |
+---------+------+------+--------------+---------------+-------------+
| 4       | 29   | 160  | 94           | 140           | 33          |
+---------+------+------+--------------+---------------+-------------+
| 4.2     |      |      | 96           | 160           | 40          |
+---------+------+------+--------------+---------------+-------------+
| 5       | 31   | 170  | 106          |               |             |
+---------+------+------+--------------+---------------+-------------+
| 6       | 33   | 180  | 119          | 237           | 50          |
+---------+------+------+--------------+---------------+-------------+
| 7       | 35   | 200  | 139          |               |             |
+---------+------+------+--------------+---------------+-------------+
| 8       | 37   | 200  | 152          | 465           | 67          |
+---------+------+------+--------------+---------------+-------------+

![](media/image8.wmf)

From Table 1, it is apparent that for the techniques recommended in the
operator manual, the SenoScan^®^ system provides dose savings that
varies from 33% for a 4-cm compressed breast to more than 67% for an
8-cm compressed breast. At 4.2-cm, the dose savings is 40%.

## 

## 

## Figure 7. SenoScan^®^ and Film-Screen mean glandular dose as a function of compressed breast thickness.

##  

The SenoScan^®^ dose was also calculated from the SenoScan^®^ tech­nique
chart provided with prototype systems used during the clinical trial.
Table 2 presents the corresponding SenoScan^®^ dose data.

> **Table 2. SenoScan^®^** dose as calculated from the technique chart
> used on clinical evaluation systems.

  ------------------------ ----------- -------------- ---------------------
  Breast Thickness, cm     kVp         mA             *SenoScan^®^ Dose,
                                                      mRad*

  2                        26          160            105

  3                        29          170            128

  4                        31          190            142

  4.2                                                 144

  5                        33          200            151

  6                        *35*        200            163

  7                        38          200            184

  8                        40          190            183
  ------------------------ ----------- -------------- ---------------------

The significantly reduced dose values for the production SenoScan^®^
system as compared to the dose values of the prototype systems used in
the clinical trials result from design changes that enabled imaging at
lower techniques with a somewhat softer beam. Dose calculations and
comparisons in Table 2 are based solely on the recommended technique
chart, and do not necessarily imply equal image quality relative to
film-screen mammography at large breast thicknesses. However, recent
research on beam optimization in digital mammog­raphy indicates that
dose-constrained image quality should not de­crease significantly as the
kVp is increased. Williams et al.[^5] suggest that for digital
mammography a figure of merit appropriate for beam optimization is
related to SNR per unit radiation dose. Using SNR2/ MGD as indicative of
image quality constrained by dose, the authors find that the performance
of all three referenced digital mammogra­phy systems (including
SenoScan^®^*)* remains fairly flat as a function of kVp.

### 

## X. Summary of Clinical Studies

Two reader studies were conducted using images acquired with the
SenoScan**^®^** system. Study A compared reader performance of digital
mammography exams printed on laser film with screen-film mammography for
the same patient. Study B compared reader performance with softcopy
diagnosis against hardcopy diagnosis (laser printed film) of digitally
acquired mammograms.

### A. Study Comparing SenoScan^®^ Full Field Digital Mammography to Screen-Film Mammography

Women were enrolled into the study at six clinical sites (Table 3). The
clinical study was designed to determine the diagnostic accuracy of the
SenoScan**^®^** system compared to standard screen-film mammography in a
population of women presenting for screening and diagnostic mammography.

1\. Study Inclusion / Exclusion Criteria

Only women who were medically eligible for screening or diagnostic
mammographic examination were included in the clinical studies. Women
who were unable or unwilling to understand or execute the patient
consent form were excluded from the study.

Digital mammography case acquisition for this study was completed in
three phases. The first phase involved the enrollment of women who had
been recommended for breast biopsy, who had had abnormal screen-film
mammograms, or who had symptoms which led to their referral for
diagnostic mammography at 4 of the participating institutions. The
second phase involved the enrollment of women who were scheduled to
undergo breast biopsy, either percutaneous or open surgical biopsy, at 2
of the participating institutions. In the third phase, cases were drawn
from the case files of two additional institutions. These mammograms
were obtained on women who were not recruited to the SenoScan**^®^**
approval trial per se, but to other clinical trials that had the same
eligibility criteria as this study at 2 participating institutions. All
of the women whose mammograms were included in Phase 3 of case
acquisition had signed consent forms that allowed the use of their
images in additional research, as needed. In total, case acquisition was
driven by the desire to obtain a representative sample from both a
screening and diagnostic population.

> **Table 3. Institutions and the phase of case acquisition in**
>
> **which they participated**

  ------------------------------------------- ---------------------------
  **Institution**                             **Phase(s)**

  University of North Carolina                1 and 2

  Sally Jobe Clinic                           1 and 2

  Brooke Army Hospital                        1

  Thomas Jefferson University                 1

  University of California at San Francisco   3

  University of Toronto                       3
  ------------------------------------------- ---------------------------

2\. Study Population

Case acquisition in the initial phase of the study was terminated when a
total of 560 women were enrolled. Additional patients were enrolled in
the next two phases of the study with the intent being to enroll
subjects until a total of 100 biopsy-proven breast cancer cases were
available for inclusion in the planned reader study.

All cases of patients with cancer were included in the reader study.
Non-cancer cases were selected by taking a stratified random sample from
the remaining cases.  The stratification was by institution, so that
cases would be included in proportion to the number of cancer cases
recruited to the protocol at each institution.  

There were 248 cases selected for inclusion in the reader study. All 248
cases consisted of both a unilateral or bilateral digital and
screen-film mammograms of the same patient. The 248 cases included 125
cases with cancer.

As the study progressed, a subset of screen-film mammograms were removed
either for patient care purposes or because the originating site
requested their return so some readers did not read all screen-film
mammograms that were initially selected for inclusion in the study. No
digital cases were removed from the reader study once it began. No
significant adverse events occurred during the film acquisition phase.

3\. Cancer Size and Stage Distribution

The Agency for Healthcare Research and Quality (formerly the Agency for
Health Care Policy and Research) Clinical Practice Guidelines, Number
13, AHCPR Publication Number 95-0632: Quality Determinants of
Mammography suggests that a good mammography program should have at
least 30% of detected cancers that are less than or equal to 1 cm in
size. With 42% of cancers being equal to or less than 1cm in size, this
study was well within the suggested guidelines. Some cancers were
positively identified as cancer via fine-needle aspiration (FNA) and
therefore no size information was available. The AHCPR guidelines
suggest that 50% of detected cancers should be Stage 0 or 1. With 75% of
cancers being stage 0 or 1, this study population fell well within this
guideline.

**Table 4. Distribution of Cancer Stages Found in the Clinical Trial
with SenoScan^^**

  ----------- ---------------- ------------- -------------- ----------------
  **Size**    **Frequency      **Percent**   **Cumulative   **Cumulative
              Count**                        Frequency**    Percent**

  **Tis**     15               20.8          15             20.8

  **T1**      11               15.3          26             36.1

  **T1A**     4                5.6           30             41.7

  **T1B**     11               15.3          41             56.9

  **T1c**     13               18.1          54             75.0

  **T2**      11               15.3          65             90.3

  **T3**      4                5.6           69             95.8

  **T4**      2                2.8           71             98.6

  **TX**      1                1.4           72             100.0
  ----------- ---------------- ------------- -------------- ----------------

4\. Image interpretation

A total of 8 radiologists participated in this reader study. Of those, 6
had extensive experience in interpreting digital mammograms. The
remaining 2 readers were trained in interpreting SenoScan**^®^** digital
mammograms by reading 10 printed digital mammograms that were not part
of this study, and receiving immediate instructive feedback regarding
pathologically proven lesions present in the images. All readers also
trained in the use of the forms used in the study just before
interpreting examinations.

The 248 digital mammograms and the 248 screen-film mammograms were
randomly assigned to one of two groups, A or B. Each group contained a
mixture of digital and screen-film examinations. If the digital
mammogram for a given patient were assigned to group A, then the
screen-film mammogram for that same patient would be assigned group B.
All readers read group A cases first. After a minimum of 4 weeks, group
B cases were then read.

The study was designed to detect differences of 0.05 in the ROC area
under the curve (AUC). The 95% confidence interval for the difference of
the mean AUC\'s (digital and film) was determined by applying the
approach described by Obuchowski in *Academic Radiology*, 1995,
2:S22-S29.

As noted by Lewin et al. In *Diagnostic Imaging 9/99,* area under the
curve, sensitivity and specificity can be affected by using suspicion of
cancer on the initial screen-film mammogram, as an enrollment criterion.
Using recruitment criteria such as a BIRADS score of 3, 4, or 5 results
in a bias towards higher sensitivity for screen-film mammography and a
higher specificity for digital mammography. The amount of bias cannot be
easily quantified.

The calculation of sensitivity and specificity was accomplished by
defining a level of suspicion (LOS) 1-5 scale used to classify the
likelihood of cancer in each case into two categories. The categories
used were LOS 1 and 2 and LOS 3, 4 and 5. The scale is as follows:

> 1 -- definitely not malignant
>
> 2 -- probably not malignant
>
> 3 -- possibly malignant
>
> 4 -- probably malignant
>
> 5 -- definitely malignant

The BIRADS standard scale for classifying was not used because of the
confounding of likelihood of cancer with "abnormality".

5\. Results

There was no statistically significant difference in the average areas
under the curve (AUC) for SenoScan**^®^** and screen-film mammography
(Table 5). The standard error and size of the confidence interval
confirmed that the study achieved the predicted power, based on the
choice of number of readers and number of cases to be included. The
true, but unknown mean difference between digital and film AUC included
zero.

Table 5. ROC Curve Comparison

+--------------+---------------+--------------+-----------------------+
|              | #####         |              |                       |
|              | Area Under RO |              |                       |
|              | C Curve (AUC) |              |                       |
+--------------+---------------+--------------+-----------------------+
|              | #             | ###### Film  | *95% CI for           |
|              | ##### Digital |              | difference in AUC's*  |
+--------------+---------------+--------------+-----------------------+
| **AVERAGE**  | .715          | .765         | (-.101, .002)         |
+--------------+---------------+--------------+-----------------------+

The average specificity of SenoScan**^®^** is somewhat higher than the
specificity of screen-film mammography (Table 6). Differences in
sensitivity and specificity are consistent with selection bias as noted
by Lewin et al.

Table 6. Sensitivity and Specificity for Film and Digital Mammograms

  -------------------------- ------------------------- ------------------
                             Film                      Digital

  **Average**                                          

  Sensitivity                0.74                      0.66

  Specificity                0.60                      0.67
  -------------------------- ------------------------- ------------------

6.  Study conclusions

The results of the study confirm that SenoScan**^®^** is safe and
effective for use in screening and diagnostic mammography. Given that
the confidence interval on the difference between areas under the curve
includes zero, SenoScan**^®^** is comparable to screen-film mammography.
No adverse events were observed.

######## Study Comparing Reader Performance with Softcopy and Hardcopy Images

This study compared the speed and accuracy of interpretations by
radiologists of SenoScan**^®^** digital mammograms displayed using two
different media: 1) laser-printed on film and 2) a softcopy workstation.

1.  Study Inclusion / Exclusion Criteria for Mammograms

SenoScan**^®^** digital mammograms were selected from University of
North Carolina case files. Digital mammograms were deemed suitable for
inclusion in this study if 1) the patient had had at least one prior
screen-film mammogram available for comparison between 10 and 65 months
previously and 2) there were a total of four standard digital mammograms
(two craniocaudal views and two mediolateral oblique views) that
included all portions of both breasts. If more than one such eligible
comparison mammogram existed, only the most recent comparison
screen-film mammogram was used in the study. Otherwise suitable digital
mammograms were excluded if they had been used in another digital
mammography reader study that was occurring at the same time as this
study, involving many of the same readers.

2.  Study Population

A total of 63 Fischer digital mammograms were identified for use in the
study. These cases contained 7 biopsy-proven cancers and 13
biopsy-proven benign lesions. The remaining cases were of 23 patients
who underwent six-month follow-up for probably benign findings and 20
cases without apparent findings. Of the 43 patients whose mammograms
were included in the study who did not undergo biopsy, 42 had normal
follow-up mammograms at one year after their study digital mammogram.
The remaining patient had an unchanged mammogram at six months after her
study digital mammogram.

3.  Demographics

The racial profile for these patients was 51 (81%) white, 9 (14%)
African American, 1 (2%) Hispanic, 1 (2%) Asian, 1 (2%) unknown. The age
breakdown of patients included in this study was 17 (26.9%) women ages
40-49 years, 23 (36.5%) women ages 50-59 years, 16 (25.4%) women ages
60-69 years, 3 (4.8%) women ages 70-79 years, 1 (1.6%) woman ages 80-89
years, and 3 (4.8%) women of undetermined age.    

4.  Image Interpretation

All readers were radiologists trained specifically in the tasks of the
study, both printed film and softcopy digital mammography
interpretation. Each reader was asked to provide his or her "hanging"
preference so that the printed and softcopy images could be displayed in
the order and site preferred by the reader.

A total of 8 other radiologist readers participated in the reader study.
Seven of the 8 readers had been trained in the interpretation of digital
mammography through participation in prior reader studies at the
University of North Carolina. The eighth reader was trained in digital
mammography interpretation using the 10 SenoScan**^®^** digital
mammogram cases included in the set of 28 printed digital mammograms
with pathologically proven lesions used to train the other readers prior
to their participation in the other study. All participating readers are
considered eligible for screen-film mammography interpretation under
Food and Drug Administration MQSA regulations.

The 63 cases were divided into two sets of cases, set A and set B, for
each of the two modalities, softcopy display and printed film, so that
there were 4 sets of cases altogether (softcopy A, printed A, softcopy
B, printed B).  Four readers read all 63 cases in softcopy first, two
readers starting with the cases in softcopy A, two readers starting with
softcopy B. Similarly, the remaining four readers read all 63 cases on
printed film first, two readers beginning with printed A, two readers
beginning with printed B.\
\
At least one month passed before each of the two groups of four readers
read the cases in the other display condition. Again, half the readers
were randomly assigned to begin with the cases in set A first.  The
other half began with set B. This counterbalancing of case display was
intended to mitigate the effects of learning and fatigue.

5.  Results

No statistically significant difference in speed or accuracy of
detection was noted. The following table shows the mean value and 95%
confidence intervals.

Table 7. Summary Results for Digital Mammograms in Hardcopy and Softcopy

  ------------- ------- ---------- ------------ ----------------------- ---------
                Film    Softcopy   Difference   Bonferroni Corrected    P Value
                                                95% Confidence          
                                                Intervals               

  AUC           0.673   0.647      0.026        -0.060 - 0.112          0.393

  Sensitivity   0.708   0.687      0.021        -0.111 - 0.153          0.598

  Specificity   0.528   0.563      -0.035       -0.243 - 0.172          0.572

  Time          1.607   1.532      0.076        -0.058 - 0.209          0.088
  ------------- ------- ---------- ------------ ----------------------- ---------

6\. Study conclusions

The results of this study demonstrated the equivalence of softcopy and
film interpretation of digital mammograms. The data suggest that viewing
times for film and softcopy mammograms are comparable. Less certainty
surrounds the diagnostic accuracy estimates because of the small sample
size, although the data exclude very large differences.

### XI. Conclusions Drawn from Nonclinical and Clinical Studies

The results of the clinical and nonclinical studies conducted by the
sponsor and described above provide a reasonable assurance of the safety
and effectiveness of the SenoScan**^®^** Full Field Digital Mammography
System for screening and diagnostic mammography. These findings
therefore support FDA approval of the Fischer SenoScan^^ Full Field
Digital Mammography System for clinical use in screening and diagnostic
mammography.

####### XII. Panel Recommendation

In accordance with the provisions of section 515(c)(2) of the act as
amended by the Safe Medical Devices Act of 1990, this PMA was not
referred to the Radiological Devices Advisory Panel, an FDA advisory
committee, for review and recommendation because the information in the
PMA substantially duplicates information previously reviewed by this
panel.

### XIII. FDA Decision

The applicant's manufacturing facility was inspected on September 20,
2001 and was found to be in compliance with the Quality Systems
Regulations. FDA issued an approval order on September 25, 2001.

### XIV. Approval Specifications

Directions for use: See the attached labeling.

Hazards to Health from Use of the Device: See Contraindications,
Warnings, Precautions and Adverse Reactions in the attached labeling.

Post-Approval Requirements and Restrictions: See approval order.

[^1]: References

    ^?^ H.H. Barrett, W. Swindell, *Radiological lmaging,* Academic
    Press, New York, 1981.

[^2]: M.M. Tesic, M. Fisher Piccaro, and B. Munier, "Full Field Digital
    Mammography Scanner," European Journal of Radiology, *Vol.* 31,
    *No.* 1, *pp.* 2-17, 1999.

[^3]: O.H. Suleiman, D.C. Spelic, J.L McCrohan, G.R. Symonds, F Hond,
    "Mammography in the 1990s: the United States and Canada," Radiology
    1999, 210:345-5 1.

[^4]: L.N. Rothenberg, "Exposures and Doses in Mammography," in
    Categorical Course in Diagnostic Radiology Physics: Physical Aspects
    of Breast Imaging **---** Current and Future Considerations, A.G.
    Haus and M.J. Yaffe, Eds. RSNA 1999, pp. 91-7.

[^5]: MB. Williams et al., *Beam Optimization for Digital Mammography,*
    in [Digital Mammography IWMD.]{.underline}