Nuclear Medicine
Early Imaging of Experimental Intestinal Infarction with 99mTc-Pyrophosphate 1 Klemens H. Barth, M.D., Philip O. Alderson, M.D., John D. Strandberg, D.V.M., and John W. Fara, Ph.D.
Extensive mucosal small-bowel infarction was produced in 8 dogs by occluding the cranial mesenteric artery. After one hour of reperfusion, 15 mCi (555 MBq) of 99mTc-pyrophosphate was intra-arterially injected into 4 dogs and venously into the other 4. Positive images were obtained in all dogs except 1 which had received an intravenous injection. Diagnostic images were obtained consistently as early as 15 minutes after injection, and the infarcted bowel could still be visualized two hours later. The average tracer content in infarcted small bowel was 0.015 % 1.0.lg. This was about eight times the uptake found in normal dogs. The results show that experimental small-bowel infarction can be detected as early as five hours after the onset of ischemia. INDEX TERMS:
Intestines, infarction. Intestines, radionuclide studies, 7 [4].1299 • (Small intestine, ischemic enteri-
tis, 7[4].266) Radiology 133:459-462, November 1979 NTREATED bowel
infarction has been reported to have a more than 90 % mortality rate (1, 2, 11). The incidence of acute mesenteric ischemia, particularly the nonocclusive type, appears to be rising, and only early recognition and treatment promise salvage. Unfortunately, clinical signs are nonspecific in the early stages, and a definitive diagnosis requires surgical exploration. Several experimental studies (3-7) have used radionuclides to diagnose mesenteric infarction. In a previous study at our laboratory (7) 99rnrc-pyrophosphate (PVP) provided positive images of mesenteric infarcts 24 hours after the ischemic insult in dogs after both arterial and venous tracer injection. The present study was undertaken to determine if early infarct detection was possible using 99mTc_PVP.
U
MATERIALS AND METHODS
Eight mongrel male dogs (14.5-16.2 kg) were studied under barbiturate anesthesia. Small-bowel infarction was induced by 4-hour balloon occlusion of the cranial mesenteric artery (CMA) as described previously (7). Care was taken to place the balloon at the level of the large collateral to the caudal mesenteric artery (Fig. 1). This resulted in consistent reduction in blood flow and allowed a more uniform distribution of infarction than in our previous study. Five hours after the start of ischemia (1 hour after release of the balloon occlusion and restoration of arterial flow), 15 mCi (555 MBq) of 99mTc_PVP 2 was injected. Four animals received the tracer via direct CMA injection, and
Fig. 1. Occlusion of the superior mesenteric artery in a dog by balloon catheter. The small balloon bulge (arrowhead) indicates occulsion of a major collateral, which is necessary to produce ischemia in the small bowel.
1 From the Russell H. Morgan Department of Radiology and Radiological Sciences, and the Division of Comparative Medicine, Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD. Presented at the Sixty-fourth Scientific Assembly and Annual Meeting of the Radiological Society of North America, Chicago, IL, Nov. 26-Dec. 1, 1978. Received May 16, 1979; accepted and revision requested June 26; received July 27. Supported in part by a Grant in Aid from The American Heart Association #M 42.2106, by U.S.P.H.S. Grant GM-10548, and by NIHGrant 1RO 1AM HL 20185-01A 1. This work represents a continuation of the authors' previous study published in Radiology 129:491-495, Nov 1978. 2 TechneScan, Mallinckrodt Inc., St. Louis, MO 63147. jr
459
460
KLEMENS
2a,b
CONTROL
H. BARTH AND OTHERS
INFARCT
15min
November 1979
CONTROL
2h
ia
20
20
Fig. 2. a. (Dog 20) Right lateral views of the abdomen 15 minutes after intra-arterial injection of 99mTc_ pyrophosphate. The control scan shows minimal background activity in the region of the intestines, whereas the infarct scan shows considerable tracer accumulation. b. At two hours background activity has almost completely cleared in the control scan, while the infarct scan shows persistance of intestinal activity. Note the reduced uptake in the ribs and spine.
3a-c
2h
18 Fig. 3. a. (Dog 18) Scan of the infarct in the right lateral and anterior positions 15 minutes after arterial injection of 99mTc-pyrophosphate, shows moderate tracer uptake in the region of the intestines. b. There is no significant change in the uptake pattern at one hour. c. At two hours there is essentially no change in the uptake pattern. Intestinal uptake contrasts better with the surrounding areas after clearing of blood from the background.
4 had peripheral venous injection. Abdominal imaging began 15 minutes after injection and continued every 15 minutes up to two hours. Anterior and lateral views (400 K) were obtained using a 19-photomu/tip/ier-tube gamma camera fitted with a high-resolution parallel-hole collimator. After imaging, the animals were killed and the peritoneal cavity opened. Ligatures were placed every 20 cm from the pylorus to the proximal colon for regional containment of the small-bowel succus. The gastrointestinal tract was then removed and washed externally. An aliquot of intestinal succus was obtained through a stab incision into the center of each 20-cm segment and counted. Specimens of the bowel wall from each segment were also counted, and the per cent 1.0./g bowel wall was determined as previously described (7). After gross pathologic examination of the entire small bowel, central sections of segmental specimens were examined for microscopic evidence of infarction. In 2 normal dogs, 15 mCi (555 MBq) 99 mTc_PYC was injected into the CMA after five hours of catheterization without balloon inflation. They were euthanized two hours later and imaging and tissue studies performed.
RESULTS
The images in the controls confirmed the absence of significant 99rrrrc_PYp uptake; high activity was seen in the skeleton, kidneys, and urinary tract (Fig. 2). Images in all 4 dogs that received intra-arterial 99mTc-PYP (Figs. 2 and 3) and 3 of the 4 dogs that received intravenous 99mTc_PYP (Fig. 4) showed increased uptake in the infarcted small bowel on the first imaging series obtained after 15 minutes (Figs. 2a, 3a, and 4a). Lesion-to-background ratios improved visually during the next 105 minutes. One of the 4 animals that received an intra-arterial injection showed a "loop" pattern at 15,60, and 120 minutes after injection. The other 3 in this group showed a diffuse pattern throughout the sequence. One animal with intravenous tracer showed a diffuse uptake pattern throughout the sequence, but in 2 dogs an initial amorphous uptake pattern changed to a loop pattern over the two-hour period. This was particularly pronounced in 1 dog (Fig. 4). In 1 dog with venous tracer, negative images were obtained throughout the two-hour period. Gross pathologic examination revealed hemorrhagic small-bowel infarction in each of the 7 animals with ab-
461
EARLY IMAGING OF INTESTINAL INFARCTION
Vol. 133
Nuclear Medicine
2h
4a-c
Fig. 4. a. (Dog 24) Infarct scan in the right lateral and anterior positions 15 minutes after intravenous injection of 99mTc-pyrophosphate showsmoderately increased uptake in the region of the intestines. b. At one houra "loop" pattern emerges on the anteriorand left lateral views. c. At two hours a pronounced "loop" hasevolved in the right lateralandanteriorviews.
TABLE
I:
Dog No.
Scintigraphic Image
Infarction Size Grade *
18. 19. 20. 27.
Positive Positive Positive Positive
III I-II II II
RESULTS OF INTRA-ARTERIAL TRACER INJECTION
Mean PerCentTracerUptake/g Normal Bowel t Infarcted Bowel+ (mean ± S.D.) (mean ± S.D.)
Large Large Large Large
0.0026 0.0015 0.0015 0.002
±0.0002 ±0.001 ±0.001 ±0.0006
0.014 0.01 0.02 0.014
±0.005 ±0.004 ±0.01 ±0.0035
Uptake Ratio: Infarct/ Normal 5/1 7/1 13/1 7/1
I = mucosal villi, II = full mucosa, III = submucosa to full wall Stomach, duodenum, andterminal ileum t 10- 14 specimens
* t
TABLE
Dog No.
Scintigraphic Image
21. 22. 24. 30.
Positive Positive Positive Negative
II:
RESULTS OF INTRAVENOUS TRACER INJECTION
Infarction Size Grade * I-II II-III III II
Large Large Large Large
Mean PerCentTracerUptake/g Normal Bowelt Infarcted Bowel+ (mean ± S.D.) (mean ± S.D.) 0.002 0.006 0.001 0.001
±0.0014 ±0.0007 ±0.001 ±0.0005
0.01 0.02 0.02 0.005
±0.006 ±0.006 ±0.008 ±0.002
Uptake Ratio: Infarct! Normal 5/1 3/1 20/1 5/1
I = mucosal villi, II = full mucosa, III = submucosa to full wall Stomach, duodenum, and terminal ileum t 10- 14 specimens
* t
normal images. The infarcts involved the entire jejunum and most of the ileum. In 2 dogs the terminal ileum and cecum were also infarcted. Histologically, hemorrhagic mucosal necrosis was found in all animals, which included the krypts in most specimens. In 6 animals the infarct extended into the submucosa and muscular layers. The grade of infarction, results of imaging, and tissue uptake of the tracer are compared in TABLES I and II. After intravenous 99mTc_PYP, images of the most advanced infarcts showed loop patterns; otherwise diffuse abdominal uptake was seen. The 1 dog with negative images after intravenous injection of the tracer had an infarction similar to those seen in animals with positive images. However, intestinal 99n1"fc_PYP uptake was significantly lower (p
Early Imaging of Experimental Intestinal Infarction with 99mTc-Pyrophosphate 1 Klemens H. Barth, M.D., Philip O. Alderson, M.D., John D. Strandberg, D.V.M., and John W. Fara, Ph.D.
Extensive mucosal small-bowel infarction was produced in 8 dogs by occluding the cranial mesenteric artery. After one hour of reperfusion, 15 mCi (555 MBq) of 99mTc-pyrophosphate was intra-arterially injected into 4 dogs and venously into the other 4. Positive images were obtained in all dogs except 1 which had received an intravenous injection. Diagnostic images were obtained consistently as early as 15 minutes after injection, and the infarcted bowel could still be visualized two hours later. The average tracer content in infarcted small bowel was 0.015 % 1.0.lg. This was about eight times the uptake found in normal dogs. The results show that experimental small-bowel infarction can be detected as early as five hours after the onset of ischemia. INDEX TERMS:
Intestines, infarction. Intestines, radionuclide studies, 7 [4].1299 • (Small intestine, ischemic enteri-
tis, 7[4].266) Radiology 133:459-462, November 1979 NTREATED bowel
infarction has been reported to have a more than 90 % mortality rate (1, 2, 11). The incidence of acute mesenteric ischemia, particularly the nonocclusive type, appears to be rising, and only early recognition and treatment promise salvage. Unfortunately, clinical signs are nonspecific in the early stages, and a definitive diagnosis requires surgical exploration. Several experimental studies (3-7) have used radionuclides to diagnose mesenteric infarction. In a previous study at our laboratory (7) 99rnrc-pyrophosphate (PVP) provided positive images of mesenteric infarcts 24 hours after the ischemic insult in dogs after both arterial and venous tracer injection. The present study was undertaken to determine if early infarct detection was possible using 99mTc_PVP.
U
MATERIALS AND METHODS
Eight mongrel male dogs (14.5-16.2 kg) were studied under barbiturate anesthesia. Small-bowel infarction was induced by 4-hour balloon occlusion of the cranial mesenteric artery (CMA) as described previously (7). Care was taken to place the balloon at the level of the large collateral to the caudal mesenteric artery (Fig. 1). This resulted in consistent reduction in blood flow and allowed a more uniform distribution of infarction than in our previous study. Five hours after the start of ischemia (1 hour after release of the balloon occlusion and restoration of arterial flow), 15 mCi (555 MBq) of 99mTc_PVP 2 was injected. Four animals received the tracer via direct CMA injection, and
Fig. 1. Occlusion of the superior mesenteric artery in a dog by balloon catheter. The small balloon bulge (arrowhead) indicates occulsion of a major collateral, which is necessary to produce ischemia in the small bowel.
1 From the Russell H. Morgan Department of Radiology and Radiological Sciences, and the Division of Comparative Medicine, Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD. Presented at the Sixty-fourth Scientific Assembly and Annual Meeting of the Radiological Society of North America, Chicago, IL, Nov. 26-Dec. 1, 1978. Received May 16, 1979; accepted and revision requested June 26; received July 27. Supported in part by a Grant in Aid from The American Heart Association #M 42.2106, by U.S.P.H.S. Grant GM-10548, and by NIHGrant 1RO 1AM HL 20185-01A 1. This work represents a continuation of the authors' previous study published in Radiology 129:491-495, Nov 1978. 2 TechneScan, Mallinckrodt Inc., St. Louis, MO 63147. jr
459
460
KLEMENS
2a,b
CONTROL
H. BARTH AND OTHERS
INFARCT
15min
November 1979
CONTROL
2h
ia
20
20
Fig. 2. a. (Dog 20) Right lateral views of the abdomen 15 minutes after intra-arterial injection of 99mTc_ pyrophosphate. The control scan shows minimal background activity in the region of the intestines, whereas the infarct scan shows considerable tracer accumulation. b. At two hours background activity has almost completely cleared in the control scan, while the infarct scan shows persistance of intestinal activity. Note the reduced uptake in the ribs and spine.
3a-c
2h
18 Fig. 3. a. (Dog 18) Scan of the infarct in the right lateral and anterior positions 15 minutes after arterial injection of 99mTc-pyrophosphate, shows moderate tracer uptake in the region of the intestines. b. There is no significant change in the uptake pattern at one hour. c. At two hours there is essentially no change in the uptake pattern. Intestinal uptake contrasts better with the surrounding areas after clearing of blood from the background.
4 had peripheral venous injection. Abdominal imaging began 15 minutes after injection and continued every 15 minutes up to two hours. Anterior and lateral views (400 K) were obtained using a 19-photomu/tip/ier-tube gamma camera fitted with a high-resolution parallel-hole collimator. After imaging, the animals were killed and the peritoneal cavity opened. Ligatures were placed every 20 cm from the pylorus to the proximal colon for regional containment of the small-bowel succus. The gastrointestinal tract was then removed and washed externally. An aliquot of intestinal succus was obtained through a stab incision into the center of each 20-cm segment and counted. Specimens of the bowel wall from each segment were also counted, and the per cent 1.0./g bowel wall was determined as previously described (7). After gross pathologic examination of the entire small bowel, central sections of segmental specimens were examined for microscopic evidence of infarction. In 2 normal dogs, 15 mCi (555 MBq) 99 mTc_PYC was injected into the CMA after five hours of catheterization without balloon inflation. They were euthanized two hours later and imaging and tissue studies performed.
RESULTS
The images in the controls confirmed the absence of significant 99rrrrc_PYp uptake; high activity was seen in the skeleton, kidneys, and urinary tract (Fig. 2). Images in all 4 dogs that received intra-arterial 99mTc-PYP (Figs. 2 and 3) and 3 of the 4 dogs that received intravenous 99mTc_PYP (Fig. 4) showed increased uptake in the infarcted small bowel on the first imaging series obtained after 15 minutes (Figs. 2a, 3a, and 4a). Lesion-to-background ratios improved visually during the next 105 minutes. One of the 4 animals that received an intra-arterial injection showed a "loop" pattern at 15,60, and 120 minutes after injection. The other 3 in this group showed a diffuse pattern throughout the sequence. One animal with intravenous tracer showed a diffuse uptake pattern throughout the sequence, but in 2 dogs an initial amorphous uptake pattern changed to a loop pattern over the two-hour period. This was particularly pronounced in 1 dog (Fig. 4). In 1 dog with venous tracer, negative images were obtained throughout the two-hour period. Gross pathologic examination revealed hemorrhagic small-bowel infarction in each of the 7 animals with ab-
461
EARLY IMAGING OF INTESTINAL INFARCTION
Vol. 133
Nuclear Medicine
2h
4a-c
Fig. 4. a. (Dog 24) Infarct scan in the right lateral and anterior positions 15 minutes after intravenous injection of 99mTc-pyrophosphate showsmoderately increased uptake in the region of the intestines. b. At one houra "loop" pattern emerges on the anteriorand left lateral views. c. At two hours a pronounced "loop" hasevolved in the right lateralandanteriorviews.
TABLE
I:
Dog No.
Scintigraphic Image
Infarction Size Grade *
18. 19. 20. 27.
Positive Positive Positive Positive
III I-II II II
RESULTS OF INTRA-ARTERIAL TRACER INJECTION
Mean PerCentTracerUptake/g Normal Bowel t Infarcted Bowel+ (mean ± S.D.) (mean ± S.D.)
Large Large Large Large
0.0026 0.0015 0.0015 0.002
±0.0002 ±0.001 ±0.001 ±0.0006
0.014 0.01 0.02 0.014
±0.005 ±0.004 ±0.01 ±0.0035
Uptake Ratio: Infarct/ Normal 5/1 7/1 13/1 7/1
I = mucosal villi, II = full mucosa, III = submucosa to full wall Stomach, duodenum, andterminal ileum t 10- 14 specimens
* t
TABLE
Dog No.
Scintigraphic Image
21. 22. 24. 30.
Positive Positive Positive Negative
II:
RESULTS OF INTRAVENOUS TRACER INJECTION
Infarction Size Grade * I-II II-III III II
Large Large Large Large
Mean PerCentTracerUptake/g Normal Bowelt Infarcted Bowel+ (mean ± S.D.) (mean ± S.D.) 0.002 0.006 0.001 0.001
±0.0014 ±0.0007 ±0.001 ±0.0005
0.01 0.02 0.02 0.005
±0.006 ±0.006 ±0.008 ±0.002
Uptake Ratio: Infarct! Normal 5/1 3/1 20/1 5/1
I = mucosal villi, II = full mucosa, III = submucosa to full wall Stomach, duodenum, and terminal ileum t 10- 14 specimens
* t
normal images. The infarcts involved the entire jejunum and most of the ileum. In 2 dogs the terminal ileum and cecum were also infarcted. Histologically, hemorrhagic mucosal necrosis was found in all animals, which included the krypts in most specimens. In 6 animals the infarct extended into the submucosa and muscular layers. The grade of infarction, results of imaging, and tissue uptake of the tracer are compared in TABLES I and II. After intravenous 99mTc_PYP, images of the most advanced infarcts showed loop patterns; otherwise diffuse abdominal uptake was seen. The 1 dog with negative images after intravenous injection of the tracer had an infarction similar to those seen in animals with positive images. However, intestinal 99n1"fc_PYP uptake was significantly lower (p
