Monitoring of Tissue Transfer Flaps by Modulated Imaging (MI) Spectroscopy

Objectives:

1. To develop a safe, non-contact, intra-operative & post-operative device, which can be
used as an adjunct to the clinical evaluation of tissue transfer flaps after
reconstructive surgery.

2. To develop an adjunctive device that can reliably detect and distinguish arterial and
venous occlusion before the clinical manifestations of such occlusions, and thus provide
the scientific basis for future studies which may use the device to potentially improve
the salvage rates after re-exploration for such complications.

3. To evaluate if changes in the optical properties of tissue transfer flaps during the
immediate post-operative period can be used to predict the development of late
complications of tissue transfer flaps, such as the development of fat necrosis and/or
flap atrophy.

Specific aims:

1. To record intra-operative and post-operative images of pedicle and free tissue transfer
flaps used in reconstructive surgery with a device that shines low energy near infrared
light that is spatially modulated into a sinusoidal configuration of amplitude called
Modulated Imaging (MI).

2. To study if the MI device described above is able to collect data regarding the optical
properties of the tissue transfer flaps, which can then be used to detect acute
post-operative occlusion of the artery or of the vein going to and from the tissue
transfer flap.

3. To study if there is a correlation between the immediate post-operative optical
properties of tissue transfer flaps and the development of late complications such as
fat necrosis and flap atrophy.

Hypotheses:

1. Prior authors have demonstrated that tissue spectroscopy can be used in both animal &
human experiments to detect and differentiate between tissue transfer flaps with
adequate vascular supply vs. flaps with either artery and/or vein occlusions prior to
the detection of such complications using standard clinical observation during the
post-operative period. These authors demonstrated that detection of the changes from
baseline values in the post-operative period of the total hemoglobin [Hb-total],
deoxygenated hemoglobin [Hb-deoxy], and oxygenated hemoglobin [Hb-O2] concentrations
using tissue spectroscopy correlated with the clinical development of arterial or venous
occlusion. 1,2 As the MI device developed at the Beckman Laser Institute has been
demonstrated to be able to detect the [Hb-total], [Hb-deoxy] and [Hb-O2] as well as the
concentration of water,[H2O] in a non-contact manner; we believe the MI device will also
be able to detect development of arterial and/ or venous occlusion in tissue transfer
flaps without requiring direct tissue contact with a tissue spectroscopy device, as was
the case with the instruments used by other authors.3, 4

2. There are higher rates of fat necrosis and flap atrophy that occur after specific types
of free tissue transfer flaps, [i.e., higher rates occur with Deep Inferior Epigastric
Perforator (DIEP) flaps vs. Transverse Rectus Abdominis (TRAM) flaps.5, 6 Some authors
have suggested that early flap congestion and the development of late fat necrosis may
be due to venous insufficiency, without complete venous occlusion 7. We hypothesize that
early post-operative changes in the flap's optical properties may be used to predict the
development of late complications such as fat necrosis and flap atrophy, as these
complications are thought to be due to a relative arterial and/or venous insufficiency
to the tissue transfer flap; and thus should be reflected in the tissue's optical
properties as detected by the MI device.

Rationale: The use of tissue pedicle and free tissue transfer flaps allows for increased
reconstructive possibilities for patients that have had disfigurement or loss of function
after trauma or oncological surgical resection. Generally, the process of creating a pedicle
tissue transfer flap involves the isolation of tissues onto a single artery and vein and then
rotating this tissue from the donor site to the site requiring reconstruction. A free tissue
transfer flap involves a process similar to the creation of a pedicle flap except that the
artery and vein going to the flap's tissues are divided and re-implanted at the site of
reconstruction. This process of using tissue transfer flaps however has known complications,
including acute complications such as arterial or venous occlusion and late complications
such as the development of fat necrosis and flap atrophy.

Acute complications involving the vascular structures of the flap can be either partial or
complete occlusion of the artery or vein going to and from the tissue flap. Both pedicle and
free tissue transfer flaps can develop severe complications if either the artery or vein is
compromised, including complete death of the tissue in the flap. If the vascular structures
going to the flap(s) are compromised then the tissues used for reconstructive surgery may
undergo damage. This tissue damage can become extensive and result in the loss of part or the
entire tissue mass in the tissue transfer flap, which in turn can result in increased
morbidity and mortality to the patient. In the reconstructive surgery literature, it has been
shown that frequent monitoring during the first 48-72 hours after reconstructive surgery
allows for early detection and intervention when a vascular compromised flap occurs. This
earlier detection then can translate into earlier interventions including surgical
re-exploration, which has been shown to improve the salvage rates of vascular compromise of
the tissue transfer flaps.8, 9 It is generally known that venous thrombosis has a worse
out-come, when compared to arterial thrombosis after surgical re-exploration and
reestablishment of blood flow. This difference between arterial and venous thrombosis is
thought to be due to the differences in the pathophysiology involved in venous congestion. In
venous thrombosis tissue fluid content is increased due to initially continued arterial
inflow, thus when venous out-flow is re-established the tissue edema continues to inhibit the
diffusion of oxygen through the interstitial space from the capillaries to the tissue cells
in the vascular beds were edema remains. The fact that venous thrombosis is more difficult to
clinically detect early may also contribute to the poorer prognosis associated with venous
thrombosis when compared to arterial thrombosis.10

Given the difficulty of early detection of venous thrombosis, and of the decreased rates of
successful salvage after surgical re-exploration for venous thrombosis, authors have employed
successfully the use of tissue spectroscopy to detect venous thrombosis several hours before
the clinical manifestations of thrombosis 2. These authors employed a spectroscopy device,
which requires direct contact with the tissues being evaluated and only provided a small
surface area in which the tissue flap's optical properties were measured. The device,
however, is able to provide both diffuse optical tomography and rapid wide-field quantitative
mapping of the tissue's optical properties in a single measurement platform through a device
that does not require direct contact with the tissues being evaluated 3, 11. As theMI device
is a new novel device developed at the Beckman laser Institute and has not been used to
evaluate human tissue transfer flaps this would be a pilot study. This pilot study would seek
to determine if this specific device is also able to detect vascular occlusion prior to
clinical detection of such occlusion, as well as to differentiate between arterial and venous
occlusions in a similar manner to other devices used by other authors, which employed tissue
spectroscopy to monitor tissue transfer flaps.

As mentioned above, delayed complications can develop after tissue transfer flaps are used in
reconstructive surgery, which include fat necrosis and flap atrophy. These late complications
are thought to be caused by a relative vascular insufficiency supplying the flaps. It is
proposed that the increased venous congestion and increased rates of fat necrosis with the
use of DIEP flaps when compared to TRAM flaps in breast reconstruction is due to a relative
venous insufficiency that is not diminished enough to cause flap loss, but is on occasion
great enough to result in the development of fat necrosis 7. The late development of flap
atrophy may also be due to a relative arterial or venous insufficiency that occurs at the
time of surgical reconstruction, and results in a relative global tissue flap ischemia
leading to the development of flap atrophy. One of the goals of this experiment is to
determine if any characteristic of the optical properties in a tissue transfer flap in the
near post-operative setting can predict the development of either fat necrosis or flap
atrophy.

The MI device is a novel unique device when compared to other spectroscopic devices used to
study tissue transfer flaps. MI uses a non-contact optical imaging technology developed at
the Beckman Laser Institute that has the unique capability of performing both diffuse optical
tomography and rapid, wide-field quantitative mapping of tissue optical properties within a
single measurement platform. While other non-contact spectroscopic devices use a
time-modulation methods, MI alternatively uses spatially modulated illumination for imaging
of tissue constituents. The MI system consists of 1) a light projection system that
illuminates the tissue with spatial sinusoid patterns, and 2) a CCD camera, which collects
the diffusely reflected light in a non-contact geometry. The wavelength of illumination can
be selected by bandpass filtering of a broadband source (i.e. tungsten lamp), or by use of a
monochromatic source (i.e. laser diode). Lastly, tissue fluorescence measurements can be
performed by placing a combination of source-blocking and bandpass emission filters in front
of the camera. 3, 11

The diffusely reflected amplitude of the modulated wave carries both optical property
(absorption, fluorescence, scattering) and depth information. Specifically, the sampling
depth of the spatially modulated wave is a function of the frequency of illumination and the
tissue optical properties. This shares many analogies to the broadband frequency-domain
photon migration (FDPM) approach. {12, 13} Consequently, measurement of multiple spatial
frequencies (periodicities) allows MI to perform two functions. First, use of a wide range of
frequency patterns allows depth-selective imaging and thus tomography of the internal 3D
tissue structure. Secondly, it can rapidly and quantitatively map optical absorption,
fluorescence yield, and scattering coefficients in near-real time, with high resolution and
over a wide field-of-view.

The ability to separate optical absorption from scattering distinguishes MI from conventional
planar reflectance imaging methods. Absorption and scattering maps can be used to
characterize the tissue's biochemical composition and structure. We have shown that these
intrinsic tissue contrast elements vary with tissue types, and their wavelength dependence
provides spectral "fingerprinting" that can be used to delineate the spatial relationships
among tissues with different optical properties and can be used to determine the amount of
H2O, [Hb-total], [Hb-deoxy], [Hb-O2] & Tissue Oxygen Saturation [StO2]. MI is able to detect
the concentration of [Hb-total], [Hb-deoxy] & [Hb-O2] in absolute amounts in units of
millimoles / unit volume of tissue measured. MI is also able to determine the percent
fraction of mass, which is comprised of H2O in terms of percent mass.11, 14. This feature is
critical to the performance of MI as a quantitative diagnostic method and, when combined with
its tomographic capabilities, underscores the uniqueness of the method, and its potential use
as a monitoring and diagnostic device to evaluate tissue transfer flaps after reconstructive
surgery.

Inclusion Criteria:

- Adult patients planned to undergo reconstructive surgery using either a pedicle or
free tissue transfer flap seen by The Plastic Surgery Service on either an in-patient
or outpatient bases.

- Adult patients that are planned to undergo reconstructive surgery as above and able to
receive information regarding the study and provide informed consent to enrollment in
the study.

Exclusion Criteria

- All emergency reconstructive surgery patients.

- Patients planned to undergo radiation therapy in the region of the reconstructive
surgery within 6 months after surgery.

- Patients who develop hypotension requiring the administration of vasopressors either
intra-operatively or during the post-operative period prior to discharge from the
hospital.

- Patients who develop clinical signs of a surgical site infection at the location of
the tissue transfer flap(s).

- Patients with the development of post-operative anemia requiring a blood transfusion
during the first 72 hours after surgery.

- Patients with tattooing or pigmented lesions on the tissue transfer flap.

- Patients who incur injury to the flaps secondary to trauma within 6 months of the
reconstructive surgery; with trauma defined as either accidental major trauma
resulting in injury to the tissue transfer flap or surgical trauma as a result of
further oncologic resection of tissues in close proximity to the tissue transfer flap.

- Minor under the age of 18 years of age.

- Patients deemed unable to comprehend and provide informed consent to enrollment into
study due to either a cognitive deficit or medical condition.