Cardiox Liver Function Test Pivotal Trial

Indocyanine green (ICG) is a water-soluble, non-toxic tricarbocyanine dye, extracted
principally by hepatic parenchymal cells and excreted almost entirely into the bile without
enterohepatic circulation. Clinically, its elimination rate is used primarily to measure
hepatic function and liver blood flow. ICG studies are also used in ophthalmic angiography
and the determination of cardiac output.

Beginning about 1959, the first human clinical studies were reported wherein an indocyanine
green (ICG) bolus was injected into a vein, and then blood samples were withdrawn over a
period of time and analyzed for ICG concentrations. This method is referred to hereinafter
as the serial blood sampling method. These blood samples are sent to a clinical laboratory
for a multi-step process of centrifuging, separation and spectrophotometric measurements of
ICG levels. The laboratory-based measured levels of residual ICG levels are then used to
determine the ICG clearance rate and R15 value or residual amount of dye remaining after 15
minutes, expressed as a percentage of the initial concentration.

As an alternative to the time- and labor-consuming serial blood sampling method, a
non-invasive technique was first reported nearly 20 years ago. In the first published
clinical study, Ishigami reported the use of a pulse dye densitometry (PDD) method to
transcutaneously detect the rate of clearance of ICG from the bloodstream to be referred to
hereinafter as dynamic liver function testing.

PDD expresses ICG elimination in terms of the indocyanine green plasma disappearance rate
because only relative ICG concentration changes are assessed. The results of this
noninvasive method have been shown to correlate with those obtained by the invasive method
used in critically ill patients (hemodynamically unstable and stable), and in patients after
liver surgery.

ICG elimination rate after liver transplantation measured by either invasive or noninvasive
ICG methods is widely used to evaluate graft function. Studies have shown that ICG
elimination, measured on the day of transplantation, reflects graft function and can be used
to predict graft viability and the expected survival of the patient. Sequential measurements
of ICG elimination between days 0 and 28 of transplantation, have been shown to predict
clinical outcome in the early postoperative period after living donor transplantation. All
of the studies have shown that the ICG elimination rate is an accurate test for evaluating
liver dysfunction, but lacks the ability to differentiate the underlying causes of the
hepatic dysfunction.

Unlike all currently existing PDD methods for performing liver function testing, LFT Dye
Monitor System employs a more sensitive method for the transcutaneous measurement of ICG
concentration level in the blood using NIR fluorescence, with a sensor that is attached
loosely to the scaphoid fossa of the ear. Thus, the chemical properties of ICG dye to
fluoresce when properly excited are used in the LFT system to enable much lower
concentrations of ICG to be detectable.

Inclusion Criteria:

1. Male or female between 18 to 75 years of age inclusive, at the time of Screening.

2. Voluntarily provide written informed consent.

3. Female patients are eligible only if all of the following apply:

- Not pregnant (negative urine pregnancy test at the Screening visit);

- Not lactating;

- Not planning to become pregnant within the duration of the study;

- Surgically sterile, or at least 2 years postmenopausal, or is practicing an
acceptable form of birth control (defined as the use of an intrauterine device,
a barrier method with spermicide, condoms, subdermal implant, oral
contraceptives, abstinence, or sterilization of monogamous partner) for greater
than 60 days prior to Screening and commits to the use of the acceptable form of
birth control for the duration of the study.

4. If a healthy volunteer; is considered to be in generally good health, in the opinion
of the Investigator, at the Screening visit based upon the results of their medical
and surgical history, vital signs, physical examination, and clinical laboratory
tests.

5. Prior to receiving any ICG injections the subject agrees to be fasting for at least
eight (8) hours.

6. If a subject with liver cirrhosis; is considered to be in general satisfactory
health, in the opinion of the Investigator (other than their hepatic impairment) at
the Screening visit based upon the results of their medical and surgical history,
vital signs, physical examination, and non-hepatic clinical laboratory tests.

7. Liver cirrhosis subjects must have a clinical diagnosis of hepatic impairment based
on documented evidence of hepatic cirrhosis by medical history, or previous liver
biopsy, or hepatic ultrasound; which conforms to the criteria for class A or B or C
of the Childs-Pugh classification (Appendix B); and are expected to require an ICG
liver function study, such as for liver transplantation, liver resection, liver
cirrhosis prognosis evaluation, functional liver cell mass and/or general liver
dysfunction evaluations.

8. On stable drug therapy that is not expected to change (i.e. in dose, frequency,
additions or deletions of agents) for at least 2 weeks before ICG dye injection.

9. Must, in the Investigator's opinion, be able to comply with study procedures.

10. If the Subject is being enrolled in the fifth group they have a diagnosis of acute
liver failure (ALF) as defined by the Principal Investigator.

Exclusion Criteria:

1. Have any clinically significant condition or unstable current illness that would, in
the opinion of the Investigator, preclude study participation or interfere with the
assessment of the procedure;

2. Known allergy or sensitivity to ICG dye or history of allergy to iodides;

3. Actively bleeding associated with acute blood volume changes.