Radiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

DOI: 10.1148/radiol.2273011673
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jaramillo, D.
Right arrow Articles by Shapiro, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jaramillo, D.
Right arrow Articles by Shapiro, F.
(Radiology 2003;227:825-832.)
© RSNA, 2003

Experimental Studies

Normal and Ischemic Epiphysis of the Femur: Diffusion MR Imaging— Study in Piglets1

Diego Jaramillo, MD, MPH, Susan A. Connolly, MD, Sridhar Vajapeyam, PhD, Richard L. Robertson, MD, Patricia S. Dunning, RTR, Robert V. Mulkern, PhD, Alison Hayward, DVM, Stephan E. Maier, MD, PhD and Frederic Shapiro, MD

1 From the Department of Radiology, Massachusetts General Hospital and Harvard Medical School, 32 Fruit St, Boston, MA 02114 (D.J.); Departments of Radiology (S.A.C., S.V., R.L.R., P.S.D., R.V.M., A.H.) and Orthopaedic Surgery (F.S.), Children’s Hospital and Harvard Medical School, Boston, Mass; and Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (S.E.M.). Received October 12, 2001; revision requested January 8, 2002; revision received August 2; accepted September 26. Supported by a Children’s Hospital Research Council Award and by grant AR42396-05 from the National Institutes of Health. Address correspondence to D.J. (e-mail: djaramillo@partners.org).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate normal diffusion characteristics in the femur in piglets and changes in diffusion with increasing duration of femoral head ischemia.

MATERIALS AND METHODS: Normal epiphyses, physes, and metaphyses of piglets were evaluated with line-scan diffusion imaging (n = 12) and diffusion-tensor imaging (n = 4). Apparent diffusion coefficient (ADC) differences between normal proximal and distal femoral structures, epiphyseal and physeal cartilage, and epiphyseal and metaphyseal marrow were compared (Mann-Whitney test). Short-term femoral ischemia was investigated after maximal abduction of the hips for 3 hours (n = 6); ADCs before and after abduction were compared (Wilcoxon signed rank test). Prolonged ischemia was investigated with placement of a ligature around the neck of a femur (n = 7); the ADC of the femur in this condition was compared (Wilcoxon signed rank test) with that of the normal contralateral femur. Changes in ADC ratios at three durations of ischemia (Kruskal-Wallis test) were compared.

RESULTS: ADC was greater in epiphyseal cartilage (mean ± 1 SD, 1.62 x 10-3 mm2/sec ± 0.38) than it was in physeal cartilage (1.28 x 10-3 mm2/sec ± 0.31) (P < .007) and greater in epiphyseal marrow (1.26 x 10-3 mm2/sec ± 0.38) than it was in metaphyseal marrow (0.91 x 10-3 mm2/sec ± 0.35) (P < .001). There was columnar arrangement of tensors in the physis. ADC decreased 26% after 3 hours of maximal abduction. After femoral neck ligature, ADC increased a mean of 27% after 6 hours and a mean of 75% after 96 hours.

CONCLUSION: Normal line-scan diffusion imaging findings indicate relative restriction of diffusion in the metaphysis and parallel orientation of tensors in the physis. Diffusion is initially restricted with decreased blood flow but increases if ischemia lasts longer.

© RSNA, 2003

Index terms: Animals • Bones, epiphyses, 44.154, 45.154 • Bones, growth and development, 44.154, 45.154 • Bones, infarction, 44.356, 45.356 • Femur, MR, 44.121411, 45.121411, 44.12143, 45.12143, 44.12144, 45.12144 • Magnetic resonance (MR), diffusion study


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Lasting epiphyseal ischemia in the growing skeleton can lead to cartilage and bone necrosis. Some of the most common conditions that lead to disability in childhood result from epiphyseal ischemia, such as Legg-Calvé-Perthes disease, or complications of treatment of developmental dysplasia of the hip. More temporary ischemia, however, may pass without sequelae. In animal models, for example, femoral epiphyseal blood flow decreases with forced hip abduction, but it can be restored without damage if the hips are returned to a normal position within 6 hours after the procedure (1).

In ischemia that causes necrosis, the main role of imaging is to determine the extent of involvement of the bone and cartilage and to depict the pattern of reperfusion. Destruction of the femoral head vascularity can lead to changes in signal intensity of the cartilage on T2-weighted magnetic resonance (MR) images that correlate with cartilaginous destruction (2). Unfortunately, T2-weighted images are sensitive only to edema of ischemic tissue, which may become apparent only days or weeks later. Dynamic MR imaging enhanced with gadopentetate dimeglumine can depict subtle femoral head ischemia in children with Legg-Calvé-Perthes disease (3) or in those treated for developmental hip dysplasia (4). In posttraumatic avascular necrosis, gadolinium-enhanced imaging also provides temporalinformation regarding the derangement of the marrow perfusion (5–7). Unfortunately, in immature hips, both ischemia that is reversible (1) and ischemia that will lead to avascular necrosis result in decreased enhancement on gadopentetate dimeglumine–enhanced images.

Diffusion-weighted imaging reflects the probing of the tissue structure by water molecules that are undergoing random diffusion-driven movements (8), and it is extremely useful in the evaluation of acute cerebral ischemia. In the first days after a stroke, diffusion-weighted imaging depicts abnormally diminished water diffusion in the infarcted tissue (9). After a week or more, as permanent tissue damage ensues, the diffusion becomes increased over normal values. Diffusion-tensor imaging reflects the direction of diffusion within the tissue, and it helps reveal the orientation of tissue structures such as white matter fibers. It is possible that diffusion-weighted imaging and diffusion-tensor imaging could be useful in the definition of the abnormal microstructure of the epiphysis and physis caused by ischemia.

We hypothesized that in the ischemic epiphysis, diffusion-weighted imaging would provide information about the duration of ischemia that is not obtainable with T2-weighted MR images or images obtained after enhancement with gadopentetate dimeglumine. Thus, we performed this preliminary study in the femoral epiphysis of the piglet to evaluate the normal characteristics of the epiphysis and the physis with diffusion-weighted imaging and diffusion-tensor imaging and the temporal sequence of changes in diffusion that occur following ischemia.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Study Design
We evaluated the normal and ischemic immature femora of 10 3-week-old piglets (Earle Parsons, Hadley, Mass) by using line-scan diffusion imaging (10). We compared apparent diffusion coefficients (ADCs) of the normal proximal and distal femoral epiphyses with those of ischemic proximal femoral epiphyses. We used two models to decrease blood flow to the hip, one transiently occluding (1) and the other permanently damaging the femoral head vascularity (2). Short-term transient ischemia in three piglets (group 1) was induced by using maximal abduction; imaging was performed in all six hips before and after 3 hours of abduction. Prolonged ischemia was induced in seven piglets (group 2) by placing a tight ligature around the right femoral head. In each of the seven animals, imaging was performed in both hips 6 hours (n = 4) and 96 hours (n = 3) after the ligature. Lack of blood flow was confirmed by using gadolinium-enhanced imaging. One proximal femur in the group in which imaging was performed at 6 hours had a destructive abnormality of that area, which was depicted incidentally; histologic analysis and findings at imaging revealed that this abnormality resembled osteomyelitis, and the femur was excluded from the study. The hospital animal care and use committee approved the study.

Normal Diffusion Characteristics of the Epiphysis, Physis, and Metaphysis
We evaluated normal diffusion in 12 hips and 12 knees: In three piglets, maximal abduction was performed, and we examined both femora prior to the procedure; in six piglets, capital femoral ligature was performed, and we examined the femur without surgery. In 3-week-old piglets, the secondary ossification centers of the proximal and distal femora are already present and well developed, and these findings are similar to those regarding the epiphyses of a 3- to 5-year-old child.

Diffusion-Tensor Imaging of Normal Epiphysis, Physis, and Metaphysis
To determine whether diffusion-tensor imaging can depict the architecture of the epiphysis and physis, we evaluated the distal femoral epiphyses without surgery in four of the piglets in group 2, and these epiphyses were harvested immediately after sacrifice. We elected to image after sacrifice to maximize resolution and avoid misregistration artifacts. To evaluate whether the diffusion of the tensors followed the longitudinal direction of the bone (as would be expected if diffusion along physeal columns is being depicted), we performed diffusion-tensor imaging at 30° intervals. The imaging data were processed to generate diffusion maps of the epiphysis and physis. These maps were correlated with available specimens of piglet epiphyses.

Transient Decreased Blood Flow Model
In piglets, continued maximal abduction of both hips results in decreased femoral head enhancement on MR images (1), and on angiograms, it results in blockage of multiple small vessels that supply the proximal femoral epiphysis (11). Both hips of three piglets were placed in the prone position, with the hips immobilized in the maximal achievable abduction against a flat surface for 2–4 hours. Imaging was performed before abduction and at the end of the abduction period. Piglets were anesthetized with an intramuscular injection of 20 mg per kilogram of body weight of ketamine hydrochloride (Ketalar; Parke-Davis, Morris Plains, NJ) and 5 mg/kg of xylazine hydrochloride (Rompun; Miles, Shawnee, Kan), which was followed by a continuous intravenous infusion of propofol 1% (Diprivan; Stuart Pharmaceuticals, Wilmington, Del) diluted in 5% dextrose at a dose of 0.002 mg/kg/min. All piglets were intubated, and pulse oximetry, heart rate, and respiratory rate were monitored during the procedure.

Long-term Decreased Blood Flow Model
This model destroys the epiphyseal vascular supply by using placement of a ligature around the vessels coursing proximally along the femoral neck (2) and leads to femoral head necrosis, which histologically resembles Legg-Calvé-Perthes disease (12). The procedure was performed by an orthopedic surgeon (F.S.). After initial induction with 20 mg/kg of intramuscularly administered ketamine hydrochloride and 5 mg/kg of xylazine hydrochloride (Miles), 3-week-old Yorkshire piglets were intubated and anesthetized with isofluorane (Aerrane; Baxter Health Care, Deerfield, Ill) at a rate of 1.5 L/min. By using a strict antiseptic technique, the lateral aspect of the right hip was incised, and dissection was continued proximally to reach the hip joint. The capsule was opened, and the joint was exposed. While the position of the femoral head within the joint was maintained, two 2-0 silk sutures were placed around the base of the femoral neck. The ligatures were tied firmly to impair the femoral neck vasculature and were left in place. The hip capsule, the overlying muscle, and the skin were closed in layers with absorbable sutures. We administered butorphanol, 0.01 mg/kg, intramuscularly for postoperative analgesia. Imaging was performed in three animals within 6 hours after surgery, and in three it was performed 96 hours after surgery.

Imaging
MR imaging was performed by using a 1.5-T system (Horizon; GE Medical Systems, Milwaukee, Wis). We examined the hips by using a pair of 10-cm receive-only surface coils (GE Medical Systems) that were placed over each hip simultaneously. Imaging was performed with the animals receiving oxygen through an endotracheal tube, and pulse oximetry monitoring was performed. The same medications were used for this procedure as were described for the abduction. Imaging was performed in the coronal plane for the abducted hips of the short-term model and in the oblique sagittal plane for the hips in the neutral position of the long-term model. With the long-term model, the images included both the proximal and the distal femur. The imaging protocol included the following sequences: intermediate-weighted fast spin-echo localizing images (repetition time msec/echo time msec, 1,300/11; echo train length, eight), fast spin-echo intermediate-weighted images (2,000/15; echo train length, eight), fast spin-echo T2-weighted images (2,000/80; echo train length, eight), and conventional spin-echo T1-weighted images (600/10). Imaging parameters included the following: field of view, 12–14 cm; section thickness, 3.0 mm; intersection gap, 1 mm; matrix size, 256 x 192; signals acquired, two. Immediately following the hand injection of gadopentetate dimeglumine (Magnevist; Berlex Laboratories, Wayne, NJ) at a dose of 0.2 mmol/kg into an ear vein, we obtained three series of contrast material–enhanced T1-weighted images (600/10) with field of view, section thickness, matrix, and signals acquired identical to those used for precontrast imaging. This sequence was optimized for spatial rather than for temporal resolution. The volume of contrast material injected ranged between 2.2 and 3.4 mL, the injection time was less than 5 seconds, and the temporal resolution of the contrast-enhanced images was approximately 180 seconds.

Line-Scan Diffusion Imaging
Prior to the administration of contrast material, diffusion-weighted images were obtained by using the line-scan method of Maier et al (10) and Robertson et al (13). With this technique, multiple diffusion-weighted spin-echo column excitations were used to construct a two-dimensional image. Line-scan diffusion imaging was used to measure diffusion in six directions, with diffusion weighting and minimal distortion due to magnetic susceptibility. We obtained images of two sagittal locations extending from the proximal to the distal femur. Parameters included a diffusion-weighting factor b of 5 and 750 sec/mm2 (with the three abduction studies) or 500 sec/mm2 (with all other studies, as the lower b factor improved signal intensity and thus image quality). Other parameters included effective repetition time msec/echo time msec of 1,520/81.6, one signal acquired, field of view of 18 x 18 cm, section thickness of 3 mm, and matrix of 256 x 256.

For diffusion-tensor imaging, characterization of the diffusion-tensor elements and anisotropic properties was performed by using sampling in six directions and providing the directional vectors (1,1,0), (-1,1,0), (1,0,1), (-1,0,1), (0,1,1), and (0,-1,1) (14). If Dxyz was the diffusion coefficient measured along the direction (x,y,z), the trace of the diffusion tensor was calculated with the following equation: trace = Dxx + Dyy + Dzz = (D110 + D101 + D011 + D-110 + D-101 + D0-11)/4.

Image Analysis
To evaluate the diffusion characteristics in the structures of the growing skeleton, a radiologist (D.J.) measured ADCs in the epiphysis and metaphysis of the abnormal proximal femur, of the normal proximal femur, and, when available, of the normal distal femur. In the studies of normal femora, when it was possible to separate between the epiphyseal cartilage and the epiphyseal ossification center, separate measurements were obtained from the epiphyseal cartilage and the marrow. In the ischemic epiphysis, however, it was not possible to differentiate accurately between the epiphyseal ossification center and the surrounding cartilage. Therefore, when we compared normal and ischemic epiphyses, a global epiphyseal value, including both the marrow and the cartilage, was obtained. The global value was used because ADC values were obtained from the line-scan diffusion images with measurement of the same region of interest in the images obtained with and without diffusion-sensitizing gradients. One of the authors (D.J.) derived ADC values with the following equation: Sb = S0e-bADC, where b is a factor of diffusion weighting, and Sb and S0 are the signal intensities with and without diffusion-sensitizing gradients, respectively.

The same observer (D.J.) compared ADC values from diffusion-weighted MR images with those from T2-weighted MR images and from T1-weighted MR images obtained after gadopentetate dimeglumine administration. Blinded to the status of the hip, the observer classified the MR appearance on T2-weighted images and on T1-weighted images obtained after gadopentetate dimeglumine administration in a binary fashion (normal vs abnormal). On T2-weighted images, the epiphysis was considered abnormal if the epiphyseal marrow or the cartilage had a signal intensity equal to or greater than that of the metadiaphysis. On T1-weighted images obtained after gadopentetate dimeglumine administration, the epiphysis was considered abnormal if the enhancement of the epiphyseal marrow or of the cartilage was less than that of the metadiaphysis. This was so because we had observed initially that nearly all T2-weighted images were normal, whereas all gadolinium-enhanced images showed lack of enhancement of the femoral head.

To compare the changes in diffusion with increasing duration and severity of ischemia, the observer obtained a ratio between the ADC of the ischemic hip and that of a normal proximal femoral epiphysis examined concurrently in the same piglet by using the following calculation: The ADC ratio was calculated by subtracting the ADC of the normal femur from the ADC of the ischemic femur and dividing the result by the ADC of the normal femur.

Statistical Analysis
Initial evaluation of the data for skewness and kurtosis revealed that the data were not distributed normally, and therefore, we used only nonparametric techniques. We compared the ADC ratios at the three time periods of ischemia; the significance of the differences was assessed by using the Kruskal-Wallis test. In the studies with bones that had not been injured, we compared the differences between the proximal and the distal structures, between the epiphyseal and the physeal cartilage, and between the epiphyseal and the metaphyseal marrow by using the Mann-Whitney test. The significance of the differences between paired observations (before and after ischemia or normal vs ischemic femoral head) in each piglet was evaluated by using the Wilcoxon signed rank test. We used statistical software (Stata; Stata, College Station, Tex), and we considered differences with a P value of less than .05 to be significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
Normal Epiphysis and Metaphysis
Line-scan diffusion imaging allowed differentiation between the cartilage of the epiphysis and the physis and between the marrow of the secondary center of ossification and of the metaphysis (Fig 1). The pooled data of 12 proximal and 12 distal femoral studies showed that ADC values were greater in the epiphyseal cartilage (mean ADC ± 1 SD, 1.62 x 10-3 mm2/sec ± 0.38) than they were in the physeal cartilage (1.28 x 10-3 mm2/sec ± 0.31) (P < .007). Similarly, ADC values were greater in the epiphyseal marrow (1.26 x 10-3 mm2/sec ± 0.38) than they were in the metaphyseal marrow (0.91 x 10-3 mm2/sec ± 0.35) (P < .001). We did not find any significant differences in ADC values between comparable structures in the proximal and the distal femur. The Table lists normal mean ADC values in the epiphyseal and physeal cartilage and in the epiphyseal and metaphyseal marrow, which are listed separately for the proximal and the distal femur. The data in the Table demonstrate that there were no significant differences between the proximal and the distal femoral ADC values in the corresponding anatomic structures.



View larger version (118K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1a. Diffusion-weighted and gadolinium-enhanced MR images of the hip in a 3-week-old piglet. The hip is presumed to be normal. (a) Sagittal diffusion-weighted image (1,520/81.6, b = 5 and 500 sec/mm2) shows a clear differentiation between epiphysis (e), physis (p), and metaphysis (m). (b) Sagittal ADC map obtained with same parameters as for a shows that the regional anatomy is more difficult to distinguish, as the epiphyseal structures are nearly isointense. e = epiphysis. (c) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) obtained immediately after the line-scan diffusion image shows that there is normal enhancement of the epiphysis and physis. Slight irregularity in epiphyseal cartilage enhancement is due to the presence of vascular canals.

 


View larger version (149K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1b. Diffusion-weighted and gadolinium-enhanced MR images of the hip in a 3-week-old piglet. The hip is presumed to be normal. (a) Sagittal diffusion-weighted image (1,520/81.6, b = 5 and 500 sec/mm2) shows a clear differentiation between epiphysis (e), physis (p), and metaphysis (m). (b) Sagittal ADC map obtained with same parameters as for a shows that the regional anatomy is more difficult to distinguish, as the epiphyseal structures are nearly isointense. e = epiphysis. (c) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) obtained immediately after the line-scan diffusion image shows that there is normal enhancement of the epiphysis and physis. Slight irregularity in epiphyseal cartilage enhancement is due to the presence of vascular canals.

 


View larger version (133K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1c. Diffusion-weighted and gadolinium-enhanced MR images of the hip in a 3-week-old piglet. The hip is presumed to be normal. (a) Sagittal diffusion-weighted image (1,520/81.6, b = 5 and 500 sec/mm2) shows a clear differentiation between epiphysis (e), physis (p), and metaphysis (m). (b) Sagittal ADC map obtained with same parameters as for a shows that the regional anatomy is more difficult to distinguish, as the epiphyseal structures are nearly isointense. e = epiphysis. (c) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) obtained immediately after the line-scan diffusion image shows that there is normal enhancement of the epiphysis and physis. Slight irregularity in epiphyseal cartilage enhancement is due to the presence of vascular canals.

 

View this table:
[in this window]
[in a new window]

  		Mean ADC Values in Normal Structures of the Immature Femur

 
Diffusion-Tensor Imaging
In the four normal specimens analyzed, diffusion-tensor imaging findings indicated a columnar arrangement of tensors in the physis and adjacent metaphysis (Fig 2). The tensors were parallel to the longitudinal axis of the bone. This columnar arrangement persisted despite rotation of the specimens. The arrangement of the tensors was random in the epiphyseal cartilage, in the epiphyseal marrow, and in the metadiaphyseal region.



View larger version (69K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2. Diffusion-weighted image (1,520/1.6, b = 5 and 500 sec/mm2) shows diffusion tensors in the distal femur of a 3-week-old piglet. Superimposed on the diffusion image are arrows indicating the direction of the tensors. The image shows the parallel pattern of diffusion of the physis and proximal metaphysis. The direction of the tensors is the same as that of the main axis of the bone. This is the same direction of the columns of the physis and metaphysis as seen on the histologic section at right.

 
Transient Decreased Blood Flow Model
With maximal abduction, there was no visible change on the diffusion-weighted images (Fig 3). However, ADC values of the entire epiphysis (including cartilage and marrow) decreased from 1.70 x 10-3 mm2/sec ± 1.70 in the neutral position (n = 6) to 1.24 x 10-3 mm2/sec ± 0.97 in maximal abduction (n = 6). Therefore, compared with values of the normal epiphyses, ADC values decreased by 26% ± 9 after short-term hip abduction (P < .001). There was no evidence of abnormality on unenhanced T2-weighted fast spin-echo images. There were areas of decreased gadolinium enhancement in the anterior femoral epiphyseal cartilage and in the marrow of the secondary ossification center compared with the enhancement of the posterior epiphysis (Fig 3b). These areas were different from those of normal inhomogeneity in epiphyseal cartilage enhancement due to vascular canals (Fig 1c) (15) and from that of marrow enhancement due to differences in marrow composition (Fig 1c) (16).



View larger version (116K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3a. Images show short-term ischemia of both femoral heads after 3 hours of maximal abduction in a 3-week-old piglet. (a) Coronal ADC map (1,520/81.6, b = 5 and 750 sec/mm2) shows the epiphyses to have uniform and symmetric signal intensity. However, ADC measurements showed that diffusion has been restricted by 12%. Arrows point to femoral heads. (b) Coronal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) obtained immediately after the line-scan diffusion image shows patchy areas of decreased enhancement in the anterior cartilage of the femoral heads (arrows) and decreased enhancement in the epiphyseal marrow on the right, both of which are consistent with ischemia.

 


View larger version (121K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3b. Images show short-term ischemia of both femoral heads after 3 hours of maximal abduction in a 3-week-old piglet. (a) Coronal ADC map (1,520/81.6, b = 5 and 750 sec/mm2) shows the epiphyses to have uniform and symmetric signal intensity. However, ADC measurements showed that diffusion has been restricted by 12%. Arrows point to femoral heads. (b) Coronal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) obtained immediately after the line-scan diffusion image shows patchy areas of decreased enhancement in the anterior cartilage of the femoral heads (arrows) and decreased enhancement in the epiphyseal marrow on the right, both of which are consistent with ischemia.

 
Long-term Decreased Blood Flow Model
In the piglets evaluated 6 hours after placement of a ligature around the femoral head (n = 4), ADC values were 1.35 x 10-3 mm2/sec ± 0.34 for the entire epiphysis on the side without surgery and 1.61 x 10-3 mm2/sec ± 0.53 on the side with surgery. This difference was not visually discernible on the ADC maps (Fig 4). In the group examined 96 hours after surgery (n = 3), diffusion-weighted studies and ADC maps showed a clear increase in signal intensity of the proximal femur, with loss of the distinction between cartilage and marrow (Fig 5). ADC values were 1.33 x 10-3 mm2/sec ± 0.25 for the femoral head without surgery and 2.28 x 10-3 mm2/sec ± 0.30 for the femoral head with surgery.



View larger version (140K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4a. Images show ischemia 6 hours after ligature of the femoral neck vessels of the contralateral hip in the piglet depicted in Figure 1. (a) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side with surgery shows slight increase in the signal intensity of the epiphysis (e) compared with that of the contralateral side. ADC was measured to be 14% greater than it was on the side without surgery. (b) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side with surgery obtained immediately after the line-scan diffusion image shows almost complete absence of enhancement of the femoral head, with only a small central enhancing area remaining.

 


View larger version (147K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4b. Images show ischemia 6 hours after ligature of the femoral neck vessels of the contralateral hip in the piglet depicted in Figure 1. (a) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side with surgery shows slight increase in the signal intensity of the epiphysis (e) compared with that of the contralateral side. ADC was measured to be 14% greater than it was on the side without surgery. (b) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side with surgery obtained immediately after the line-scan diffusion image shows almost complete absence of enhancement of the femoral head, with only a small central enhancing area remaining.

 


View larger version (191K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 5a. Images show long-term ischemia 96 hours after ligature of the femoral neck vessels in a 3-week-old piglet. (a) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side without surgery shows the epiphysis (e) and metaphysis (m) to be nearly isointense. (b) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side without surgery obtained immediately after the line-scan diffusion image shows that there is normal enhancement of the epiphysis and physis (p). The center of the ossification normally has delayed enhancement because it is less vascular and has more fatty marrow. (c) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side with surgery shows marked increase in the signal intensity of the epiphysis (e) compared with that of the contralateral side. ADC was measured to be 98% greater than it was on the side without surgery. (d) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side with surgery obtained immediately after the line-scan diffusion image shows complete absence of enhancement of the femoral head. T2-weighted image (not shown) obtained concurrently was normal.

 


View larger version (147K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 5b. Images show long-term ischemia 96 hours after ligature of the femoral neck vessels in a 3-week-old piglet. (a) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side without surgery shows the epiphysis (e) and metaphysis (m) to be nearly isointense. (b) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side without surgery obtained immediately after the line-scan diffusion image shows that there is normal enhancement of the epiphysis and physis (p). The center of the ossification normally has delayed enhancement because it is less vascular and has more fatty marrow. (c) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side with surgery shows marked increase in the signal intensity of the epiphysis (e) compared with that of the contralateral side. ADC was measured to be 98% greater than it was on the side without surgery. (d) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side with surgery obtained immediately after the line-scan diffusion image shows complete absence of enhancement of the femoral head. T2-weighted image (not shown) obtained concurrently was normal.

 


View larger version (169K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 5c. Images show long-term ischemia 96 hours after ligature of the femoral neck vessels in a 3-week-old piglet. (a) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side without surgery shows the epiphysis (e) and metaphysis (m) to be nearly isointense. (b) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side without surgery obtained immediately after the line-scan diffusion image shows that there is normal enhancement of the epiphysis and physis (p). The center of the ossification normally has delayed enhancement because it is less vascular and has more fatty marrow. (c) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side with surgery shows marked increase in the signal intensity of the epiphysis (e) compared with that of the contralateral side. ADC was measured to be 98% greater than it was on the side without surgery. (d) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side with surgery obtained immediately after the line-scan diffusion image shows complete absence of enhancement of the femoral head. T2-weighted image (not shown) obtained concurrently was normal.

 


View larger version (163K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 5d. Images show long-term ischemia 96 hours after ligature of the femoral neck vessels in a 3-week-old piglet. (a) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side without surgery shows the epiphysis (e) and metaphysis (m) to be nearly isointense. (b) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side without surgery obtained immediately after the line-scan diffusion image shows that there is normal enhancement of the epiphysis and physis (p). The center of the ossification normally has delayed enhancement because it is less vascular and has more fatty marrow. (c) Sagittal ADC map (1,520/81.6, b = 5 and 500 sec/mm2) of the side with surgery shows marked increase in the signal intensity of the epiphysis (e) compared with that of the contralateral side. ADC was measured to be 98% greater than it was on the side without surgery. (d) Sagittal gadolinium-enhanced T1-weighted spin-echo MR image (600/10) of the side with surgery obtained immediately after the line-scan diffusion image shows complete absence of enhancement of the femoral head. T2-weighted image (not shown) obtained concurrently was normal.

 
Intermediate and T2-weighted images showed no abnormality in the piglets imaged within 6 hours after surgery. Of the three piglets imaged 96 hours after surgery, only one showed a mild increase in signal intensity of the marrow on T2-weighted images. Images obtained in all six hips with surgery after gadolinium-based contrast agent administration demonstrated global decreased epiphyseal enhancement compared with that of the contralateral normal epiphysis. Although the low signal intensity involved the entire epiphysis, the physis was spared. There was no difference between gadolinium-enhanced images obtained 6 and 96 hours after surgery (Figs 4, 5). There were no abnormalities detected at the histologic examination of the specimens.

Time-dependent Changes in Diffusion
Figure 6 shows the changes in ADC with increasing duration of ischemia. Compared with the normal epiphyses, ADC values decreased by 26% ± 9 (mean ± 1 SD) after short-term hip abduction. After femoral neck ligation, ADC values increased a mean of 27% ± 3 after 6 hours and a mean of 75% ± 20 after 96 hours (P < .001, Kruskal-Wallis test).



View larger version (13K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 6. Graph of percentage change in ADC following 3 hours of abduction and 6 and 96 hours of femoral neck ligature. Diffusion is restricted with milder shorter ischemia, is mildly increased with short-term severe ischemia, and is markedly increased with long-term severe ischemia.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
 
The study results show that line-scan diffusion-weighted imaging can provide additional information regarding the normal and ischemic femoral epiphysis, physis, and metaphysis. Findings in studies with line-scan diffusion show differences in normal diffusion among the epiphysis, the physis, and the metaphysis, and diffusion-tensor imaging findings show that diffusion in the intact physis is oriented in the direction of the chondrocyte columns. As in the brain, decreased perfusion initially restricts diffusion of water molecules, but prolonged lack of blood flow results in increased diffusion. Although gadolinium-enhanced images showed a striking absence of normal enhancement, the findings varied little (at least during the first 96 hours) with the duration of the ischemia. Diffusion-weighted images, on the other hand, showed a clear temporal sequence. Further work is necessary to discern whether diffusion imaging provides more temporal information than does gadolinium-enhanced imaging, whether the transition from restricted to increased diffusion signifies irreversible epiphyseal damage, and whether diffusion-tensor imaging can help to demonstrate a disturbed columnar structure of the physis.

Cartilage and marrow in the epiphysis had significantly greater ADC values than did physeal cartilage and metaphyseal marrow. If diffusion decreases as the extracellular space diminishes, as in the brain (17), it is clear that a more cellular tissuelike metaphyseal hematopoietic marrow or physeal cartilage should have lower ADC values. Findings in previous articles showed contradictory results regarding the influence of cellularity in the marrow. Although Baur et al (18) and Herneth et al (19) showed that malignant cellularity decreased diffusion, Castillo et al (20) suggested that it had no substantial effect. Nonomura et al (21), who studied humans of different ages, indicated a positive correlation between ADC value and bone marrow cellularity, with fatty marrow having more restricted diffusion. It is not clear why our results differ from those of Nonomura et al (21). We used a technique that is less affected by magnetic susceptibility, and we performed imaging by using a larger b factor (22). Even within our series, although in the first few studies we used a b factor of 750 sec/mm2, we soon realized that the images obtained with a b factor of 500 sec/mm2 were more adequate because of the gain in signal intensity. The lower b factor should decrease our sensitivity to diffusion but increase the influence of perfusion (23); perfusion-corrected diffusion-weighted MR imaging may help in elucidating the contribution of regional differences in blood flow to the diffusion differences observed (24).

The parallel arrangement of the tensors in the physis and adjacent metaphysis suggests that the direction of the tensors reflects the columnar architecture of this region. It is possible that, in growing bones, diffusion occurs preferentially along the palisade-like arrangement of the physis and primary spongiosa of the metaphysis. Diffusion of water is markedly restricted in cartilage, mostly by collagen fibers (25), which in the physis are parallel to the columns of chondrocytes. Persistence of the columnar tensor arrangement along the longitudinal axis of the bone despite changes in position suggests that the finding is real. The apparent depiction of physeal and metaphyseal columns raises the possibility of using this technique to detect the subtle physeal derangements that precede abnormal growth. The ability of diffusion-tensor imaging to depict musculoskeletal structures has been demonstrated in the intervertebral disk (25).

Epiphyseal ischemia is common in children. It accounts for many growth abnormalities and premature arthrosis related to developmental dysplasia of the hip and Legg-Calvé-Perthes disease and is also the most important complication of acute hip effusions, slipped capital femoral epiphysis, and fractures of the femoral neck (26–28). The epiphyseal ischemia in some of these conditions is eminently treatable if the lack of blood flow is diagnosed early. Ischemia in developmental dysplasia of the hip results exclusively from excessive abduction during treatment (29)—decreasing the degree of abduction is believed to restore normal blood flow (30). In joint effusions, joint aspiration usually reverses the ischemia. In some of the conditions in which epiphyseal ischemia is not treatable, such as Legg-Calvé-Perthes disease, it may be important to assess the duration of ischemia and the extent of epiphyseal damage. Diffusion-weighted imaging may be of help in these conditions because it can depict abnormal diffusion suggestive of ischemia without the use of intravenous contrast material and because it can provide an estimate of the duration of the insult. It is possible that findings of diffusion-weighted imaging may suggest whether ischemic damage is reversible, but further research is necessary to clarify this point.

Diffusion-weighted MR imaging in the skeleton has been limited mostly to evaluation of neoplasms (18,31). Diffusion-weighted imaging has relied mostly on echo-planar imaging techniques; artifacts related to magnetic susceptibility, chemical shift, and motion, however, limit echo-planar imaging in the skeleton (13,32,33). Line-scan diffusion imaging is not based on echo-planar imaging and is thus only minimally degraded by these artifacts. We believe that line-scan diffusion imaging is therefore much better suited for evaluation of diffusion in the bones and cartilage. Our models resulted in decreased perfusion to the epiphyseal marrow; the findings, therefore, are applicable to avascular necrosis of the hip in the mature skeleton.

The time course of diffusion changes probably reflects restriction of diffusion by cytotoxic edema initially and tissue destruction leading to increased diffusion later. This explanation is similar to that for changes in brain diffusion following stroke (9). Since diffusion-weighted imaging of cartilage is sensitive to changes in tissue structure (34,35), the increase in diffusion after 96 hours may reflect the early breakdown of the cartilaginous matrix components with ischemia. The time course of the diffusion changes observed in the hip was faster than that observed in the brain, because the ADC in stroke only increases after 2 days in experimental animals and later in humans (17).

This is a preliminary study with a small number of animals. The ultimate issue of whether ischemia with increased diffusion is irreversible is extremely complex, and our data are insufficient to settle it. It is important to evaluate long-term changes in diffusion related to ischemia. The spatial resolution of the images is not comparable to that of conventional imaging, and, therefore, it is difficult to reliably differentiate between cartilage and marrow, which is why we report a global epiphyseal ADC. It is also important to perform a more in-depth comparison between the diffusion-tensor imaging results and the normal and abnormal histologic findings.

Diffusion-weighted MR imaging and diffusion-tensor imaging reveal structural characteristics of the epiphysis, the physis, and the metaphysis and can help differentiate between short-and long-term changes following interruption of blood flow to the epiphysis. In the proximal femoral epiphysis, decreased blood flow leads to an initial decrease in ADC, but it later results in progressively increased ADCs. Although the changes are less conspicuous than those of gadolinium-enhanced images, they indicate the duration of the insult and possibly the extent of tissue damage due to decreased blood flow.

Practical application: If findings in further studies demonstrate that diffusion-tensor imaging does indeed reflect the columnar architecture of the physis, diffusion-tensor imaging could be used as a tool for early detection of many growth disorders, including those resulting from ischemia. The changes in diffusion with increasing duration of epiphyseal ischemia may provide information not only about the presence of ischemia but also about whether ischemia has resulted in irreversible tissue damage.


   FOOTNOTES
 
Abbreviation: ADC = apparent diffusion coefficient

Author contributions: Guarantors of integrity of entire study, D.J., S.A.C., F.S.; study concepts, D.J. S.A.C., R.L.R., S.V., R.V.M., S.E.M., F.S.; study design, D.J., S.A.C., F.S.; literature research, D.J., S.V., R.V.M., F.S.; experimental studies, D.J., S.A.C., P.S.D., A.H., R.L.R., S.E.M., F.S.; data acquisition, D.J., S.A.C., P.S.D., A.H., R.L.R., S.V., F.S.; data analysis/interpretation, D.J., S.A.C., S.V., R.L.R., R.V.M., F.S.; statistical analysis, D.J.; manuscript preparation, editing, revision/review, and final version approval, D.J., S.A.C., F.S.; manuscript definition of intellectual content, D.J., S.A.C., R.L.R., S.V., R.V.M., S.E.M., F.S.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 

  1. Jaramillo D, Villegas-Medina OL, Doty DK, et al. Gadolinium-enhanced MR imaging demonstrates abduction-caused hip ischemia and its reversal in piglets. AJR Am J Roentgenol 1996; 166:879-887.[Abstract/Free Full Text]
  2. Babyn PS, Kim HK, Gahunia HK, et al. MRI of the cartilaginous epiphysis of the femoral head in the piglet hip after ischemic damage. J Magn Reson Imaging 1998; 8:717-723.[Medline]
  3. Sebag G, Ducou Le Pointe H, Klein I, et al. Dynamic gadolinium-enhanced subtraction MR imaging: a simple technique for the early diagnosis of Legg-Calvé-Perthes disease—preliminary results. Pediatr Radiol 1997; 27:216-220.[CrossRef][Medline]
  4. Jaramillo D, Villegas-Medina O, Laor T, Shapiro F, Millis MB. Gadolinium-enhanced MR imaging of pediatric patients after reduction of dysplastic hips: assessment of femoral head position, factors impeding reduction, and femoral head ischemia. AJR Am J Roentgenol 1998; 170:1633-1637.[Abstract/Free Full Text]
  5. Munk PL, Lee MJ, Janzen DL, et al. Gadolinium-enhanced dynamic MRI of the fractured carpal scaphoid: preliminary results. Australas Radiol 1998; 42:10-15.[Medline]
  6. Lang P, Mauz M, Schorner W, et al. Acute fracture of the femoral neck: assessment of femoral head perfusion with gadopentetate dimeglumine-enhanced MR imaging. AJR Am J Roentgenol 1993; 160:335-341.[Abstract/Free Full Text]
  7. Vande Berg BE, Malghem JJ, Labaisse MA, Noel HM, Maldague BE. MR imaging of avascular necrosis and transient marrow edema of the femoral head. RadioGraphics 1993; 13:501-520.[Abstract]
  8. Le Bihan D, Mangin JF, Poupon C, et al. Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging 2001; 13:534-546.[CrossRef][Medline]
  9. Provenzale JM, Sorensen AG. Diffusion-weighted MR imaging in acute stroke: theoretic considerations and clinical applications. AJR Am J Roentgenol 1999; 173:1459-1467.[Abstract]
  10. Maier SE, Gudbjartsson H, Patz S, et al. Line scan diffusion imaging: characterization in healthy subjects and stroke patients. AJR Am J Roentgenol 1998; 171:85-93.[Abstract/Free Full Text]
  11. Barnewolt CE, Jaramillo D, Taylor GA. Correlative imaging evaluation of abduction-induced hip ischemia in piglets (abstr). Radiology 1997; 205(P):275.
  12. Kim HK, Su PH, Qiu YS. Histopathologic changes in growth-plate cartilage following ischemic necrosis of the capital femoral epiphysis: an experimental investigation in immature pigs. J Bone Joint Surg Am 2001; 83:688-697.[Abstract/Free Full Text]
  13. Robertson RL, Maier SE, Robson CD, Mulkern RV, Karas PM, Barnes PD. MR line scan diffusion imaging of the brain in children. AJNR Am J Neuroradiol 1999; 20:419-425.[Abstract/Free Full Text]
  14. Basser PJ, Pierpaoli C. A simplified method to measure the diffusion tensor from seven MR images. Magn Reson Med 1998; 39:928-934.[Medline]
  15. Barnewolt CE, Shapiro F, Jaramillo D. Normal gadolinium-enhanced MR images of the developing appendicular skeleton. I. Cartilaginous epiphysis and physis. AJR Am J Roentgenol 1997; 169:183-189.[Abstract/Free Full Text]
  16. Dwek JR, Shapiro F, Laor T, Barnewolt CE, Jaramillo D. Normal gadolinium-enhanced MR images of the developing appendicular skeleton. 2. Epiphyseal and metaphyseal marrow. AJR Am J Roentgenol 1997; 169:191-196.[Abstract/Free Full Text]
  17. Schaefer PW, Grant PE, Gonzalez RG. Diffusion-weighted MR imaging of the brain. Radiology 2000; 217:331-345.[Abstract/Free Full Text]
  18. Baur A, Stabler A, Bruning R, et al. Diffusion-weighted MR imaging of bone marrow: differentiation of benign versus pathologic compression fractures. Radiology 1998; 207:349-356.[Abstract/Free Full Text]
  19. Herneth AM, Philipp MO, Naude J, et al. Vertebral metastases: assessment with apparent diffusion coefficient. Radiology 2002; 225:889-894.[Abstract/Free Full Text]
  20. Castillo M, Arbelaez A, Smith JK, Fisher LL. Diffusion-weighted MR imaging offers no advantage over routine noncontrast MR imaging in the detection of vertebral metastases. AJNR Am J Neuroradiol 2000; 21:948-953.[Abstract/Free Full Text]
  21. Nonomura Y, Yasumoto M, Yoshimura R, et al. Relationship between bone marrow cellularity and apparent diffusion coefficient. J Magn Reson Imaging 2001; 13:757-760.[CrossRef][Medline]
  22. Yoshiura T, Wu O, Zaheer A, Reese TG, Sorensen AG. Highly diffusion-sensitized MRI of brain: dissociation of gray and white matter. Magn Reson Med 2001; 45:734-740.[CrossRef][Medline]
  23. Le Bihan D. Molecular diffusion nuclear magnetic resonance imaging. Magn Reson Q 1991; 7:1-30.[Medline]
  24. van Rijswijk CS, Kunz P, Hogendoorn PC, Taminiau AH, Doornbos J, Bloem JL. Diffusion-weighted MRI in the characterization of soft-tissue tumors. J Magn Reson Imaging 2002; 15:302-307.[CrossRef][Medline]
  25. Hsu EW, Setton LA. Diffusion tensor microscopy of the intervertebral disc anulus fibrosus. Magn Reson Med 1999; 41:992-999.[CrossRef][Medline]
  26. Kalamchi A, MacEwen GD. Avascular necrosis following treatment of congenital dislocation of the hip. J Bone Joint Surg Am 1980; 62:876-888.[Abstract/Free Full Text]
  27. Jaramillo D, Kasser JR, Villegas-Medina OL, Gaary E, Zurakowski D. Cartilaginous abnormalities and growth disturbances in Legg-Calvé-Perthes disease: evaluation with MR imaging. Radiology 1995; 197:767-773.[Abstract/Free Full Text]
  28. Kaniklides C. Diagnostic radiology in Legg-Calvé-Perthes disease Uppsala, Sweden: Uppsala University, 1996.
  29. Keret D, MacEwen GD. Growth disturbance of the proximal part of the femur after treatment for congenital dislocation of the hip. J Bone Joint Surg Am 1991; 73:410-423.[Abstract/Free Full Text]
  30. Ramsey PL, Lasser S, MacEwen GD. Congenital dislocation of the hip: use of the Pavlik harness in the child during the first six months of life. J Bone Joint Surg Am 1976; 58:1000-1004.[Abstract/Free Full Text]
  31. Lang P, Wendland MF, Saeed M, et al. Osteogenic sarcoma: noninvasive in vivo assessment of tumor necrosis with diffusion-weighted MR imaging. Radiology 1998; 206:227-235.[Abstract/Free Full Text]
  32. Melhem ER. Technical challenges in MR imaging of the cervical spine and cord. Magn Reson Imaging Clin N Am 2000; 8:435-452.[Medline]
  33. Baur A, Stabler A, Huber A, Reiser M. Diffusion-weighted magnetic resonance imaging of spinal bone marrow. Semin Musculoskelet Radiol 2001; 5:35-42.[CrossRef][Medline]
  34. Burstein D, Gray ML, Hartman AL, Gipe R, Foy BD. Diffusion of small solutes in cartilage as measured by nuclear magnetic resonance (NMR) spectroscopy and imaging. J Orthop Res 1993; 11:465-478.[CrossRef][Medline]
  35. Donahue KM, Weisskoff RM, Burstein D. Water diffusion and exchange as they influence contrast enhancement. J Magn Reson Imaging 1997; 7:102-110.[Medline]



This article has been cited by other articles:


Home page
 Biophys. JHome page
R. M. Williams, W. R. Zipfel, M. L. Tinsley, and C. E. Farnum
Solute Transport in Growth Plate Cartilage: In Vitro and In Vivo
Biophys. J., August 1, 2007; 93(3): 1039 - 1050.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
N. M. Menezes, S. A. Connolly, F. Shapiro, E. A. Olear, R. M. Jimenez, D. Zurakowski, and D. Jaramillo
Early Ischemia in Growing Piglet Skeleton: MR Diffusion and Perfusion Imaging
Radiology, January 1, 2007; 242(1): 129 - 136.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jaramillo, D.
Right arrow Articles by Shapiro, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jaramillo, D.
Right arrow Articles by Shapiro, F.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
RADIOLOGY RADIOGRAPHICS RSNA JOURNALS ONLINE