Survey of complications of indocyanine green angiography in Japan

PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.     

Digital indocyanine green angiography in chorioretinal diseases

BACKGROUND: Fluorescein angiography (FA) is important in the diagnosis of chorioretinal diseases; however, it has some limitations. We conducted this study to evaluate whether digital indocyanine green (ICG) angiography can offer enhanced image in chorioretinal diseases. METHODS: Digital indocyanine green angiography with scanning laser ophthalmoscope (SLO) was performed in 314 patients with various chorioretinal diseases. This coupled digital imaging system can offer instant images, process and store data by computer, and give convenient hardcopy generation. RESULTS: The digital ICG angiography provided enhanced image resolution of the choroid compared with FA. The disease categories included choroidal neovascularization (CNV), choroidal tumor, inflammatory choroidal disease, ischemic choroidal disorder, idiopathic central serous chorioretinopathy and retinal macroaneurysm. CONCLUSIONS: ICG angiography is a useful adjunctive diagnostic technique to fluorescein angiography for various chorioretinal diseases. It is especially useful in the diagnosis of occult and recurrent CNV, as well as choroidal tumor and choroiditis. With greater clinical experience, ICG angiography is promising in giving additional clinical information for many other chorioretinal diseases.     

Role of indocyanine green fluorescence videoangiography in evaluation of subretinal disease

BACKGROUND: Indocyanine green (ICG) is a sterile, water-soluble, tricarbocyanine dye that can be used in fundus angiography as an adjunct to sodium fluorescein. It has a peak spectral absorption of 805 nm in blood plasma or blood, as compared with fluorescein, which has a peak spectral absorption of 465 nm. Because the absorption and emission of ICG lies around 835 nm, transmission of energy by the retinal pigment epithelium (RPE) and serosanguinated material is more efficient in this region than in the region of visible light energy. ICG has the property of being approximately 98% bound to blood protein, disallowing extravasation of excessive dye in the highly fenestrated choroidal vasculature. METHODS: The characteristics of ICG are discussed, including administration and dosage, adverse reactions and use of infrared filters for fundus photography. In addition, two cases are presented to illustrate the clinical application of ICG for diagnosis and treatment of choroidal neovascular membranes. RESULTS: ICG videoangiography can be used to reveal subfoveal choroidal neovascular membranes not previously identified with fluorescein; angiograms can also be used to dramatically highlight retinal and choroidal changes. CONCLUSIONS: The use of ICG for fundus videoangiography provides a more accurate and complete evaluation in certain cases of subretinal and choroidal disease.     

Improvement by FUB 181, a novel histamine H3-receptor antagonist, of learning and memory in the elevated plus-maze test in mice

PURPOSE: Initial experimental results of contrast-enhanced pulmonary MR angiography using the new superparamagnetic iron oxide blood pool agent FeO-BPA. METHOD: Pulmonary MRA was performed in 7 domestic pigs using a cardiac-triggered coronal T1-weighted FFE-Sequence before and up to 90 minutes after contrast injection obtained on a 1.5 T magnet with a standard gradient equipment. A dose of 4 mg Fe/kg bodyweight was used for MRA. The images were qualitatively assessed and compared with X-ray i.v.-DSA. RESULTS: The injection of FeO-BPA allows the acquisition of unsaturated in-plane images of the pulmonary vascular tree down to the first order subsegmental branches including vessel diameters of approximately 1.5 mm. In the normal non-occluded vasculature, no signal void is seen in the TE range of 2.8-5.5 ms secondary to exceeding susceptibility effects which are caused by the iron oxide accumulation. Even 90 minutes after injection of FeO-BPA, assessment of the pulmonary vasculature is still satisfactory. CONCLUSIONS: In the animal experiment, the use of the blood pool agent FeO-BPA provides detailed pulmonary angiograms even on a magnet with a conventional gradient system. The major advantage is the comfortable diagnostic window of > 1.5 hours which also portends its utility for future MR-guided pulmonary interventions.     

Indocyanine green angiography in choroidal osteoma

BACKGROUND: Choroidal osteoma is a rare choroidal tumor; knowledge of its indocyanine green characteristics is limited. METHODS: The fundus photographs and the fluorescein and indocyanine green angiograms of three patients were reviewed. Each patient was examined at least twice with a follow-up varying from 10 to 60 months. RESULTS: Late-phase fluorescein angiograms allow assessment of the extension of the osteoma as it is variably hyperfluorescent due to tumor staining combined with a variable degree of overlying retinal pigment epithelial changes. The hypofluorescent area observed in the early phase of the indocyanine green angiogram corresponds with the extent of the osteoma but the borders may be difficult to demarcate. In the late phase of the indocyanine green angiogram, hypofluorescence due to choriocapillaris loss and hyperfluorescence due to leakage from abnormal choroidal vessels are combined. Infrared angiography high-lights abnormal choroidal vessels and vascular spiders present on the tumor surface. It is difficult to differentiate these choroidal vascular anomalies from subretinal neovascularization. CONCLUSIONS: We find no homogeneous pattern either on fluorescein or on infrared angiography. The findings may change with follow-up, indicating changes within the tumor or the surrounding tissue that are still poorly understood.     

The identity of the previous visitor influences flower rejection by nectar-collecting bees

PURPOSE: To compare subtracted and nonsubtracted gadolinium-enhanced magnetic resonance (MR) angiography and cardiac-synchronized time-of-flight MR angiography for help in detecting pelvic-region stenoses. MATERIALS AND METHODS: Twenty-eight patients with intermittent claudication underwent MR angiography with a 1.5-T system; two-dimensional cardiac-synchronized time-of-flight MR angiograms and three-dimensional MR angiograms (without and with gadolinium enhancement) were obtained. Subtracted images were obtained by subtracting unenhanced data from enhanced data of identical volumes, and maximum intensity projection images were constructed, which two observers independently evaluated in blinded fashion, with conventional angiographic results as the reference standard. RESULTS: Sensitivity and specificity for grading of hemodynamically significant stenoses (> or = 50% lumen reduction) on subtracted MR angiograms were 94% and 93%, respectively. Sensitivity of subtracted images was significantly higher compared with that of time-of-flight images (P < .05) but not with that of nonsubtracted images. Contrast-to-noise ratio on subtracted images was significantly higher compared with that on nonsubtracted images (P < .05) but not with that on time-of-flight images. There was good correlation between stenosis length measurements on gadolinium-enhanced MR angiograms and those on conventional angiograms. CONCLUSION: Subtracted MR angiography is superior to cardiac-synchronized time-of-flight MR angiography for imaging of iliac and upper femoral arteries and provides higher contrast-to-noise ratio, fewer artifacts, and easier image interpretability than nonsubtracted MR angiography.     

Visualization of leukocyte dynamics in the choroid with indocyanine green

PURPOSE: To report a method to evaluate leukocyte dynamics in the choroidal circulation with indocyanine green (ICG) angiography. METHODS: Nonpigmented and pigmented rats were administered ICG solution intravenously. The fundus image was obtained with a scanning laser ophthalmoscope and recorded on magnetic tapes at a video rate (30 frames/second). The images were analyzed with a personal computer-based image analysis system. RESULTS: On ICG angiography, hyperfluorescent dots were seen moving along the choroidal vessels and in the retinal vessels several minutes after injection. These fluorescent dots were thought to be circulating leukocytes stained with ICG. The micrographs of blood smears after ICG injection showed intense fluorescence of leukocytes. Computer-assisted image analysis allowed tracing of these fluorescent dots using a frame-by frame method. CONCLUSIONS: Results of this study indicated that ICG can be used for vital staining of leukocytes and that it is possible to evaluate leukocyte movement in the choroidal circulation in vivo in rats.     

Reduction of hippocampal-kindled seizure activity in rats by stereotactic radiosurgery

The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5')-tetraphosphate) and its analogue 99mTc AppCHClppA for imaging experimental atherosclerotic lesions in New Zealand White rabbits. Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides. After acquiring the final images, the animals were sacrificed, ex vivo images of the aortas were recorded, and biodistribution was measured. 99mTc-Ap4A and 99mTc AppCHClppA accumulated rapidly in atherosclerotic abdominal aorta, and lesions were clearly visible within 30 min after injection in all animals that were studied. Both radiopharmaceuticals were retained in the lesions for 3 hr, and the peak lesion to normal vessel ratio was 7.4 to 1. Neither of the purine analogs showed significant accumulation in the abdominal aorta of normal (control) rabbits. The excised aortas showed lesion patterns that were highly correlated with the in vivo and ex vivo imaging results. The present study demonstrates that purine receptors are up-regulated in experimental atherosclerotic lesions and 99mTc-labeled purine analogs have potential for rapid noninvasive detection of plaque formation.     

Effects of brovincamine fumarate on choroidal blood volume in rabbits]

We examined the effects of brovincamine fumarate, a Ca(2+)-channel blocker, on choroidal blood flow. We measured the choroidal blood volume continuously for 1 hour using laser Doppler flowmetry, as well as systemic blood pressure, heart rate, and intraocular pressure in six urethane-anesthetized rabbits after intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine. As a control, ten rabbits receiving no medication were used. All the data were recorded and analyzed using MacLab on a computer. In both the 0.1 mg/kg and 0.5 mg/kg brovincamine-injected groups, the choroidal blood volume decreased significantly after administration, but showed no significant difference from controls. Vascular resistance in the choroid showed a significant increase over the value before administration and over the control group. The heart rate decreased significantly compared to the value before injection and to the control group. The mean blood pressure in both dose groups and the intraocular pressure in the 0.5 mg/kg injected group were significantly higher than the controls. These results indicate that intravenous administration of 0.1 mg/kg or 0.5 mg/kg brovincamine does not cause an increase in the choroidal blood volume in urethane-anesthetized rabbits.     

Value of image subtraction in 3D gadolinium-enhanced MR angiography of the renal arteries

The objective of this study was to evaluate quantitatively and qualitatively the effect of image subtraction on the image quality of three-dimensional (3D) gadolinium-enhanced MR angiograms of the renal arteries. Breath-hold 3D gadolinium MR angiography (MRA) as well as conventional contrast angiography of the renal arteries was performed on 20 patients with suspected renovascular hypertension. MR angiograms were acquired before and during dynamic infusion of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). Contrast-enhanced images were compared with images that had undergone voxel-by-voxel signal intensity subtraction of contrast-enhanced data from precontrast data. One false positive finding for significant renal artery stenosis was recorded with MRA using conventional angiography as the gold standard. Image subtraction did not alter the diagnosis at MRA in any case. The mean contrast-to-noise ratio (CNR) was significantly higher (P < .05) on the subtraction MR angiograms compared to the nonsubtracted MR angiograms. There was no significant difference in the signal-to-noise ratio (SNR). Qualitative analysis revealed a significant improvement in image quality after image subtraction with respect to visualization of the distal renal arteries. In conclusion, image subtraction improves the quality of renal MRA in terms of both CNR and visualization of the distal renal arteries.     

Diagnosis of disease of the common carotid artery bifurcation: CT angiography vs catheter angiography

OBJECTIVE: The purpose of this prospective study was to compare CT angiography with conventional catheter angiography for imaging the bifurcation of the common carotid artery in patients with signs and symptoms of atherosclerotic disease. SUBJECTS AND METHODS: Ten symptomatic patients (20 bifurcations of the common carotid artery) underwent contrast-enhanced spiral CT of the neck. The images were preprocessed and postprocessed by using a commercially available volume-rendering technique and a maximum-intensity-projection algorithm. All patients subsequently underwent conventional catheter angiography. RESULTS: CT angiographic findings matched those on conventional angiograms in only 50% of cases. Two nearly occluded internal carotid arteries were missed with CT angiography. Four internal carotid arteries were interpreted as occluded on the basis of CT angiograms but were shown as patent on catheter angiograms. Of five severe stenoses shown by CT angiography, only two were confirmed by conventional angiography. CONCLUSION: The results indicate that CT angiography as used in this study cannot replace catheter angiography. With CT angiography, both overestimation and underestimation of stenoses occur.     

Idiopathic polypoidal choroidal vasculopathy of the macula

OBJECTIVE: The authors evaluated the clinical, fluorescein, and indocyanine green (ICG) angiographic characteristics of the macular variant of idiopathic polypoidal choroidal vasculopathy (IPCV). DESIGN: Observational case series. PARTICIPANTS: The records, photographs, and fluorescein and ICG angiograms of eight eyes of seven patients with IPCV lesions confined to the macula were reviewed. MAIN OUTCOME MEASURES: The visual acuity, fundus examination, fluorescein and ICG angiographic characteristics, and clinical course were compared. RESULTS: All patients demonstrated polypoidal lesions arising from macular choroidal vessels on ICG angiography. One patient had bilateral lesions. These lesions appeared hyperfluorescent in the early phases of both fluorescein and ICG angiography. Late-phase leakage was seen in cases associated with subretinal fluid or exudate. None of these patients demonstrated polypoidal lesions arising from the peripapillary choroidal circulation or peripapillary choroidal neovascularization. Three eyes with polypoidal lesions that were associated with subretinal fluid and exudates were treated with photocoagulation. Five eyes were not treated. Final visual acuity ranged from 20/20 to hand motions. Severe visual loss was associated with vitreous and subretinal hemorrhage, but this resolved without permanent severe visual loss in several cases. CONCLUSIONS: In the macular variant of IPCV, ICG and fluorescein angiography demonstrate characteristic macular polypoidal lesions without evidence of peripapillary lesions. The vascular origin of these polypoidal lesions appears to be the macular choroidal circulation. This is distinguished from classic IPCV, in which lesions appear to arise from the peripapillary choroidal circulation. Visual prognosis appears to be good, with most patients retaining visual acuity of 20/80 or better. If subretinal fluid or exudates reduce visual acuity, photocoagulation should be considered.     

Atherosclerotic renal artery stenosis: ostial or truncal?

PURPOSE: To evaluate a discrepancy between the location of renal artery stenoses on intraarterial digital subtraction angiographic (DSA) images and that on spiral computed tomographic (CT) angiograms. MATERIALS AND METHODS: The spiral CT angiograms and intraarterial DSA images of 40 consecutive patients with atherosclerotic renal artery stenoses were examined retrospectively. Stenoses were classified as truncal or ostial. The atherosclerotic changes in the abdominal aorta were graded. RESULTS: Fifty-eight stenoses were demonstrated. In 48 ostial stenoses, there was no discrepancy in the location of the stenoses on spiral CT angiograms and DSA images. In 10 patients, spiral CT angiography showed an ostial lesion, whereas DSA demonstrated an apparent truncal lesion. Most of these stenoses ("pseudotruncal" ostial stenoses) were in patients with severe aortic atherosclerotic disease. CONCLUSION: A renal artery stenosis at or within 10 mm of an atherosclerotic aorta at DSA may be diagnosed as an ostial stenosis.     

Procreation after death or mental incompetence: medical advance or technology gone awry?

PURPOSE: To study the feasibility of using an iodinated particulate contrast agent, iodipamide ethyl ester (IDE), for angiography. MATERIALS AND METHODS: IDE at doses of 40-100 mg of iodine per kilogram was diluted to a total volume of 5-20 mL and used for digital subtraction angiography in nine dogs under general anesthesia. Equivalent images were obtained by using water-soluble contrast medium (WSCM) for comparison (iohexol) in seven animals. All images were reviewed by blinded reviewers and graded subjectively on a five-point scale. RESULTS: Angiographic studies of multiple vascular territories performed with IDE yielded images of slightly lower overall quality compared with images obtained with WSCM (P = .14, Mann-Whitney U test). Arterial phase images were subjectively superior with WSCM when compared with IDE (P < .0001, chi 2.) Depiction of the corresponding veins during the venous phase on the IDE angiograms was superior to that on WSCM angiograms in 12 of 21 cases, although this did not reach statistical significance (P > .05 chi 2). Images of the renal vein and portal vein achieved with IDE were graded as superior to those achieved with WSCM in eight of 10 reviews. CONCLUSION: Angiography is feasible with IDE. Compared with WSCM, IDE produced images of lesser quality during the arterial phase, but of equal or superior quality in the venous phase depending on the vessel studied. Because it is excreted slowly in bile and is isotonic, it may prove useful in patients with renal insufficiency, diabetes, multiple myeloma, or severe coronary disease.     

Ulcerative colitis with overexpression of p53 preceding overt histological abnormalities of the epithelium

Laser-induced fluorescence of pheophorbide a (Ph-a) was used for in vitro photodynamic imaging (PDI) of a rat pancreatic acinar tumor. A 400 nm excitation induced a 470 nm autofluorescence and a 678 nm dye fluorescence in tumors and their surrounding pancreas 24 h after a 9 mg kg-1 body weight Ph-a intravenous administration. With lower intensities in these blood-rich tumors than in pancreas, Ph-a fluorescence signals are unable to provide tumor images. A dimensionless function (the ratio of Ph-a fluorescence by autofluorescence, called Rt for the tumor and Rp for the pancreas) was used for fluorescence contrast calculation (C = Rt/Rp) between six tumors and their paired pancreas. Among five available laser excitation wave-lengths, only the 355 nm excitation gave a distinctive contrast (C = 1.5). The PDI of six intrapancreatic tumors and their intraperitoneal metastasis and of two control normal pancreas was thus performed ex vivo using a 355 nm excitation source delivered by a tripled Nd:YAG laser and a charged-coupled device camera. Fluorescence images were recorded at 680 nm (dye), 640 nm (background) and 470 nm (autofluorescence) through three corresponding 10 nm width bandpass filters. Computed division for each pixel of Ph-a fluorescence values by autofluorescence generated false color image. In this way, contrasted tumor images were obtained. But in five out of six animals false-positive images were present due to an autofluorescence decrease in some normal pancreatic areas. A 470 nm autofluorescence imaging on the same tumors gave in all cases false-positive image and false-negative in half of the cases. These observations suggest that autofluorescence alone is unable to achieve accurate PDI of pancreatic carcinoma and that using Ph-a as a PDI dye needs strong improvements.     

Radiosurgery and microsurgery for AVMs

We developed a method of velocity-coded color MR angiography using a color code from the data obtained from velocity-phase images of phase-contrast MR angiography in order to add flow direction information to MR angiograms. Phase-contrast MR angiography with reconstruction of velocity-phase images was performed in 30 patients. Two projection images from velocity-phase images of each phase-contrast MR angiogram were obtained and assigned color according to flow direction. We then superimposed the two color images onto the maximum intensity projection image of the MR angiogram. The velocity-coded color MR angiogram clearly showed flow direction from the data on the phase-contrast MR angiogram of the neck. Veins were readily distinguishable from arteries, and flow changes, such as a subclavian steal, were also identified.     

Medical care employment in the United States, 1968 to 1993: The importance of health sector jobs for African Americans and women

OBJECTIVE: To compare helical computed tomography angiography with arterial digital subtraction angiography in the diagnosis of renal artery stenoses. METHODS: Fifty hypertensives (24 men; mean age 53 years) were prospectively studied with computed tomography (Somaton Plus S, Siemens) and digital angiography (double-blind evaluation). Computed tomography was performed both in the sequential (the length of the abdomen) and in the helical (6 cm around renal arteries) modes during injection of 120 cm3 contrast medium. RESULTS: Digital angiography visualized 16 significant (< 50% on quantitative angiography) stenoses (16/131 renal arteries, including 32 accessory), in 14 (28%) patients. On helical computed tomography, 16 stenoses were detected, in 49 patients (16/122 renal arteries, seven accessory arteries were not identified because they were located out side the scan area); two patients had false-positive helical computed tomography results. The computed tomography sensitivity, specificity, positive and negative predictive values were 87.5% (14/16), 98.2% (111/114), 87.5% and 98.2%, respectively. In the sequential mode, two cases of bilateral adrenal hyperplasia, two aortic aneurysms and one renal neoplasm were detected. None of these patients had renal artery stenosis. CONCLUSIONS: Helical computed tomography is a suitable new non-invasive diagnostic modality for the detection of renal artery stenosis or adrenal pathology. With continued development and evaluation computed tomography could prove useful as a screening tool or as a replacement for digital angiography in patients with possible secondary hypertension.     

Diagnosis of pulmonary embolism with magnetic resonance angiography

BACKGROUND: Diagnosing pulmonary embolism may be difficult, because there is no reliable noninvasive imaging method. We compared a new noninvasive method, gadolinium-enhanced pulmonary magnetic resonance angiography, with standard pulmonary angiography for diagnosing pulmonary embolism. METHODS: A total of 30 consecutive patients with suspected pulmonary embolism underwent both standard pulmonary angiography and magnetic resonance angiography during the pulmonary arterial phase at the time of an intravenous bolus of gadolinium. All magnetic resonance images were reviewed for the presence or absence of pulmonary emboli by three independent reviewers who were unaware of the findings on standard angiograms. RESULTS: Pulmonary embolism was detected by standard pulmonary angiography in 8 of the 30 patients in whom pulmonary embolism was suspected. All 5 lobar emboli and 16 of 17 segmental emboli identified on standard angiograms were also identified on magnetic resonance images. Two of the three reviewers reported one false positive magnetic resonance angiogram each. As compared with standard pulmonary angiography, the three sets of readings had sensitivities of 100, 87, and 75 percent and specificities of 95, 100, and 95 percent, respectively. The interobserver correlation was good (k=0.57 to 0.83 for all vessels, 0.49 to 1.0 for main and lobar vessels, and 0.40 to 0.81 for segmental vessels). CONCLUSIONS: In this preliminary study, gadolinium-enhanced magnetic resonance angiography of the pulmonary arteries, as compared with conventional pulmonary angiography, had high sensitivity and specificity for the diagnosis of pulmonary embolism. This new technique shows promise as a noninvasive method of diagnosing pulmonary embolism without the need for ionizing radiation or iodinated contrast material.     

Rectovaginal septum adenomyotic nodules: a series of 500 cases

PURPOSE: Selective mesenteric angiography is an expensive, invasive, diagnostic, and therapeutic tool for lower gastrointestinal hemorrhage. Some institutions have required a positive nuclear medicine bleeding scan before angiography. We have attempted to determine if this is a valid screening test for mesenteric angiography. Are there any other factors to predict which patients are actively bleeding and who will benefit from angiography? METHODS: All cases of mesenteric angiography for hemorrhage performed during a 12-year period were reviewed. RESULTS: A total of 131 angiograms were performed during a 12-year period with 45 patients demonstrating active bleeding; 54 patients had a bleeding scan before angiography. A positive bleeding scan did not increase the percentage of positive angiograms. A history of prior gastrointestinal bleeding, transfusions, orthostatic hypotension, or tachycardia were not predictors for a positive angiogram. DISCUSSION: This study could not identify any single useful predictor that will increase the likelihood of obtaining a positive angiogram. Nuclear medicine scans should not be used routinely as a screening test for angiography.     

Influence of diagnostic and treatment factors in the population pharmacokinetics of gentamicin

STUDY OBJECTIVES: To determine the feasibility of macroscopic visualization of small ovarian cancer metastases in vivo by fluorescence after intravenous administration of 5-aminolevulinic acid (ALA); to assess the time after drug injection when fluorescence of small metastases is maximum; and to correlate macroscopic in vivo fluorescence with both microscopic ex vivo fluorescence and histologic findings. DESIGN: Controlled animal study (Canadian Task Force classification I). SETTING: University-based facility. SUBJECTS: Twenty-four healthy, female Fischer rats. INTERVENTION: Diffuse peritoneal metastatic cancer was induced in Fischer 344 rats by intraperitoneal injection of 1 million syngeneic ovarian cancer cells (NuTu-19). Four weeks after induction ALA100 mg/kg was injected intravenously, and diagnostic laparotomy was performed 1, 3, 6, or 9 hours thereafter. MEASUREMENTS and MAIN RESULTS: The peritoneal cavity was illuminated with the Wood's lamp (ultraviolet light). Fluorescence was determined by direct visualization and compared with a calibrated fluorescent disk. Tissues were collected, sectioned, and examined by fluorescence and conventional light microscopy. Within 1 to 3 hours after intravenous injection of ALA, in vivo fluorescence of tumor nodules (diameter 0.4-5.0 mm) was macroscopically visible. Tumor-free peritoneum did not show fluorescence and was significantly distinguishable from cancer nodules. Fluorescence from intestinal tissues was comparable with tumor nodules. Microscopic fluorescence analysis showed similar values for tumor nodules and peritoneum. Stained histologic specimens of peritoneal surface revealed a superficial layer of cancer cells responsible for fluorescence. The time course of the fluorescence curve in the intestine peaked twice, at 1 and 6 hours after ALA injection. Macroscopically fluorescing nodules were histology confirmed as malignant. CONCLUSIONS: Fluorescence detection of small cancer nodules after intravenous injection of ALA is feasible for nodules smaller than 0.5 mm on the peritoneum. One to 3 hours after drug injection is optimal for diagnosis of metastases.