Abdominal ultrasonography is a routinely performed, noninvasive method for evaluating hepatic parenchyma. However, many parenchymal changes have a similar appearance,1 and the accuracy of ultrasonography as the sole criterion for discriminating among the categories of diffuse liver disease of cats is < 60%.2 The prevalence of chronic kidney disease reportedly was very high in a group of randomly selected cats (37.5% to 42.1%, depending on the age).3 Similar to the description for the liver, ultrasonographic findings for various infiltrative renal diseases have a similar appearance,4 which limits the diagnostic accuracy of the technique.
In veterinary medicine, the availability of cross-sectional imaging modalities is increasing, and the use of such modalities to assess the liver and kidneys is garnering interest. Magnetic resonance imaging of the parenchymatous abdominal organs is an important tool for the detection and characterization of focal and generalized lesions. In addition to the morphological evaluation of structures (typically by assessment of unenhanced T1-weighted, T2-weighted, and contrast-enhanced T1-weighted images), the use of functional imaging techniques such as PW-MRI and DW-MRI to provide additional information is gaining popularity.
Literature on MRI of the abdominal organs of cats is scarce. Morphological information for MRI images obtained by use of a 1.5-T system for a group of healthy cats has been described,5 but the literature is lacking functional data. Magnetic resonance cholangiopancreatography has been described for 10 cats with cholangitis and pancreatitis.6
To the authors’ knowledge, diffusion and perfusion of the liver, spleen, and kidneys of cats have not been described. Therefore, the objective of the study reported here was to describe the PW-MRI and DW-MRI characteristics of parenchymatous organs and structures in the cranial aspect of the abdomen of healthy adult cats. These data could be used as baseline information for evaluation of pathological conditions and investigation of the diagnostic potential of these techniques.
Materials and Methods
Animals
Twelve adult neutered male shorthair cats specifically bred for experimental studies were enrolled in the study. Mean ± SD age was 89.2 ± 0.8 months (range, 87 to 90 months), and mean body weight was 4.5 ± 0.4 kg (range, 3.6 to 5.3 kg). All cats were considered in good health on the basis of results of a physical examination, hematologic evaluation, and biochemical analysis. Cats were classified as ASA I, except for 2 cats that had elevated renal values and were classified as International Renal Interest Society state 2 and, therefore, ASA II. All study procedures were reviewed and approved by the Cantonal Veterinary Office of Zurich (ZH118–16).
Anesthesia and instrumentation of cats
Food was withheld from the cats for 12 hours. Each cat then was premedicated by IM administration of ketamine hydrochloride (10 mg/kg), midazolam (0.1 mg/kg), and butorphanol tartrate (0.3 mg/kg). A catheter was aseptically placed in a cephalic vein for administration of gadolinium and medications. Oxygen was administered via a face mask for 30 minutes prior to anesthesia induction. Anesthesia was induced with alfaxalone (0.5 to 2 mg/kg, IV), and the trachea was intubated with a cuffed endotracheal tube, which was connected to a rebreathing system. Anesthesia was maintained with isoflurane in a mixture of oxygen and air (1:1). Each cat was mechanically ventilated by use of positive pressure with a pressure-controlled mode (5 to 11 cm H2O); the respiratory rate was adjusted to achieve an end-tidal partial pressure of CO2 of 35 to 42 mm Hg. Lactated Ringer solution (3 mL/kg/h) was administered throughout anesthesia. Anesthesia monitoring included cardiovascular and respiratory variables, which were measured continuously and recorded by use of a multiparameter monitor that included a spirometer, capnograph, MRI-compatible wireless respiratory sensor, vectorcardiograph, and pulse oximeter (the probe was placed on the dog's tongue). If pulse rate decreased to < 100 beats/min for more than 10 minutes, glycopyrrolate (10 μg/kg, IV) was administered. When necessary, administration of glycopyrrolate was repeated once.
MRI
Each cat was positioned in dorsal recumbency and scanned by use of a 3-T MRI systema with a phased-array anterior coil.b Morphological imaging included a transverse scan of the cranial aspect of the abdomen on T2-weighted (turbo spin echo; repetition time, 1,250 milliseconds; echo time, 80 milliseconds; flip angle, 90°; field of view, 220 mm; voxel size, 0.60/0.73/3.00 mm; slice thickness, 3 mm; and slice gap, 0.3 mm) and T1-weighted (multiecho Dixon, gradient echo; repetition time, 10 milliseconds; echo time, 3.5 milliseconds; flip angle, 15°; field of view, 250 mm; voxel size, 1.31/1.21/3.00 mm; slice thickness, 3 mm; and slice gap, 0.5 mm) images. Functional sequences performed included DW-MRI (3b imaging performance sensitivity encoding; repetition time, 1,301.5 milliseconds; echo time, 66.7 milliseconds; flip angle, 90°; field of view, 250 mm; voxel size, 2.98/3.13/3.00 mm; slice thickness, 3 mm; slice gap, 0.5 mm; number of directions, 4; and number of b values, 3 [0, 300, and 600]; obtained on the transverse plane). The T1 PW-MRI sequences were performed successively (multitransmit-enhanced high-resolution isotropic volume examination; dynamic parallel imaging performance sensitivity encoding; T1 multiecho Dixon, gradient echo; repetition time, 3.1 milliseconds; echo time, 1.5 milliseconds; flip angle, 10°; field of view, 280 mm; voxel size, 1.49/1.51/3.00 mm; slice thickness, 3 mm; slice gap, −1.5 mm; and number of dynamics, 6). Contrast mediumc (0.3 mL/kg, IV) was manually injected during the third scan, which was followed by IV injection of 10 mL of saline (0.9% NaCl) solution. Several anesthetists, all of whom were experienced and specifically trained and instructed, performed the injections. Finally, an additional T1-weighted (multiecho Dixon, gradient echo; repetition time, 10 milliseconds; echo time, 3.5 milliseconds; flip angle, 15°; field of view, 250 mm; voxel size, 1.31/1.21/3.00 mm; slice thickness, 3 mm; and slice gap, 0.5 mm) sequence was performed.
A breath-hold technique was used for T1-weighted precontrast and postcontrast MRI, whereas free breathing was used for the T2-weighted MRI, DW-MRI, and PW-MRI. For the breath-hold technique, controlled mechanical ventilation was intermittently discontinued to allow expiratory apnea to develop. Immediately after 1 sequence was obtained, controlled mechanical ventilation was resumed until an end-tidal partial pressure of CO2 of 35 mm Hg was achieved. This stabilization period minimized the likelihood of spontaneous respiration during the subsequent breath-hold sequence. Duration of the stabilization period differed among sequences and cats. Dynamic sequences were performed with free breathing.
Processing of MRI data
All MRI data were processed on an extended workstation.d Quantitative ADC maps were derived from the DW-MRI scans. The ADC images were assessed qualitatively and quantitatively. For the quantitative evaluation, several ROIs were manually drawn on the various structures. Three ROIs were drawn on the liver (1 each on the left, right, and middle parts of the hepatic parenchyma in areas with homogenous SI). Care was taken to ensure that large blood vessels and the gallbladder were not included in ROIs. Two ROIs were drawn on the splenic parenchyma (one in the dorsal extremity and the other in the ventral extremity); care was used to avoid large blood vessels and boundaries of the organ. The ADCs were calculated for both the hepatic and splenic parenchyma; the mean value was determined for the corresponding ROIs. For each cat, the ADC for the liver was normalized by dividing the ADC for the hepatic parenchyma by the ADC for the splenic parenchyma.
Three ROIs were drawn on the cortex of each kidney (1 in the dorsal region, 1 in the middle region, and 1 in the ventral region). An additional ROI was drawn on the medulla of each kidney, where it was visible as a higher SI, compared with the SI for the cortex.
For the dynamic PW-MRI images of each cat, 10 ROIs were manually drawn and propagated through all scans. These ROIs were located as follows: 2 on the hepatic parenchyma, 2 on the splenic parenchyma (typically a region on each of the dorsal and ventral extremities), 2 on the renal cortex (1 each for the right and left kidneys), 2 on the renal medulla (1 each for the right and left kidneys), and 2 on the paralumbar (epaxial) musculature (1 each for the right and left sides). When drawing these ROIs, care was used to avoid large blood vessels, the gallbladder, and boundaries of the structures.
For each ROI, the workstation software generated an SI-versus-time curve (ie, time-intensity curve). Other variables generated for each ROI of the PW-MRI images included maximum enhancement, maximum relative enhancement, time to peak SI, uptake rate, washout rate, brevity of enhancement, and area under the time-intensity curve. Maximum enhancement was the difference between initial intensity and peak intensity and measured in arbitrary units. Relative enhancement was a measure of signal enhancement of a pixel in the PW-MRI scan, compared with signal enhancement for that pixel in an MRI scan obtained prior to administration of contrast medium. Maximum relative enhancement was the maximum for all relative enhancements over all dynamics. Time to peak SI was the time from the start of the scan until maximum SI was detected. Uptake rate was the maximum slope between the time of onset of contrast medium inflow and time of peak intensity. Washout rate was the maximum slope between the time of peak intensity and time that the contrast medium was eliminated. Brevity of enhancement represented the time between the maximum uptake rate and maximum washout rate. Area under the time-intensity curve represented the sum of all intensities. For each cat, ratios were calculated wherein each perfusion variable for a given ROI was divided by the corresponding variable for the skeletal muscle.
Statistical analysis
Descriptive data were generated by use of a commercially available software program.e Results were reported as median and range. The ADC values of the various ROIs for each structure were compared with each other by use of a 1-way repeated-measures ANOVA. The ADC values were tested for significant differences among the structures by use of the Wilcoxon signed rank test. Values were considered significant at P < 0.05.
Results
Structure and SI of the liver were considered clinically normal on all morphological images of the 12 cats. Visual assessment of T2-weighted images revealed that the SI of the liver was homogenously hypointense, compared with that of the spleen. The SI of the liver was isointense, compared with that of epaxial muscle, in 5 cats and mildly hyperintense in 7 cats.
Visual assessment of T2-weighted images revealed that the shape and structure of the kidneys were abnormal in the 2 cats classified as ASA II. Data relative to the kidneys for these 2 cats were excluded from the study. In 3 of the remaining 10 cats, there were minimal irregularities of the renal surface; however, the kidneys were considered morphologically normal despite this finding. In these cats, the kidneys had a smooth surface with good definition of the cortex and medulla. Visual assessment of T2-weighted images revealed that the renal cortex was homogeneously hyperintense, compared with muscle and liver, and hypointense, compared with the spleen.
Visual assessment of precontrast T1-weighted images revealed that SI of the liver was homogeneously and mildly hyperintense, compared with that of the epaxial muscles and spleen. For the 10 aforementioned cats, SI of the renal cortex was homogeneously hyperintense (compared with the muscle, medulla, and spleen) and isointense (compared with the liver) in 3 cats; isointense (compared with the muscle), hyperintense (compared with the spleen), and hypointense (compared with the liver) in 4 cats; hyperintense (compared with the muscle and spleen) and hypointense (compared with the liver) in 2 cats; and hypointense (compared with the muscle and liver) and hyperintense (compared with the spleen) in 1 cat. In all 10 cats, the cortex was hyperintense, compared with the medulla.
During the dynamic contrast-enhanced scan, the liver had early enhancement and the spleen had an arciform pattern of enhancement5 in all cats. Enhancement of the kidneys was typically progressive and centripetal, beginning at the outer rim of the renal cortex and progressing from the renal cortex into the medulla in all cats.
Evaluation of postcontrast T1-weighted images revealed that the liver was the structure with the highest SI in all cats, except for 1 in which it was isointense, compared with the spleen. In all cats, cortices of the kidneys had a thin and even rim of a high-intensity signal in the region of the capsule with a hypointense underlying cortex. Cortices of the kidneys were subjectively isointense (compared with the liver) in 6 cats and mildly hypointense (compared with the liver) in 4 cats. In all cats, the medulla was hyperintense, compared with the cortex. Epaxial muscle had the lowest SI for all sequences and all cats (Figure 1).
Representative T2-weighted images (A and D), T1-weighted precontrast images (B and E), and T1-weighted postcontrast images with fat suppression (C and F) obtained from a cat and used for visual assessment of the SI of abdominal organs and structures. Ventral is at the top of each image, and the right side of the cat is to the left of each image.
Citation: American Journal of Veterinary Research 80, 2; 10.2460/ajvr.80.2.159
Evaluation of the PW-MRI SI curve indicated that the hepatic peak was the earliest peak in 10 cats, immediately after the renal peak in 1 cat, and concurrent with the renal medulla peak in 1 cat. The PW-MRI SI of the hepatic peak was lower than the splenic peak in 10 cats and higher than the splenic peak in 2 cats. The PW-MRI SI of the splenic parenchyma peak was the latest peak in 5 cats and concurrent with or earlier than the renal peak in 7 cats. The PW-MRI SI of the splenic parenchyma peak was the highest peak in 6 cats, lower than the renal peak in 4 cats, and between the renal cortex peak and medulla peak in 2 cats. The PW-MRI SI of the renal cortex peak was after the hepatic peak in 7 cats, at the same time as the splenic peak in 1 cat, the latest peak in 1 cat, and the earliest peak in 1 cat. The PW-MRI SI of the renal cortex peak was the highest in 2 cats, higher than the splenic peak but lower than the medulla peak in 2 cats, and lower than the splenic peak and medulla The PW-MRI SI of the medulla peak was the last peak in 3 cats, later than the cortex peak in 3 cats, earlier than the cortex peak in 3 cats, and concurrent with the cortex peak in 1 cat. The PW-MRI SI of the medulla peak was the highest in 4 cats, lower than the renal cortex peak in 2 cats, and higher than the cortex peak but lower than the splenic peak in 4 cats.
The SI of the epaxial musculature was consistent among cats. It was the lowest SI with a flat curve that slowly increased over time to form a plateau. Typical time-intensity curves that indicated the time when the various peaks appeared and the SI during the dynamic contrast-enhanced scan were created (Figure 2).
Graph of time-intensity curves that depict signal enhancement over time for the ROIs of the liver (squares), spleen (circles), renal cortex (black triangles), renal medulla (white triangles), and epaxial musculature (diamonds) for a representative cat.
Citation: American Journal of Veterinary Research 80, 2; 10.2460/ajvr.80.2.159
Median and range values of PW-MRI variables for the liver, spleen, renal cortex, renal medulla, and epaxial muscle were summarized (Table 1). Median and range values for the ratio of each PW-MRI variable for each structure (liver, spleen, renal cortex, and renal medulla), compared with the corresponding PW-MRI variable for the epaxial muscle, were similarly summarized (Table 2). Transverse plane T1 PW-MRI images were used to evaluate ROIs (Figure 3).
Median (range) values for selected PW-MRI variables for each of 5 ROIs for 10 healthy adult male cats.
| Variable* | Hepatic parenchyma | Splenic parenchyma | Renal cortex | Renal medulla | Epaxial muscle |
|---|---|---|---|---|---|
| Relative enhancement (%) | 99.38 (61.44–130.51) | 154.78 (92.43–256.23) | 170.09 (109.19–233.12) | 201.62 (115.98–285.77) | 27.12 (17.45–35.19) |
| Maximum enhancement (arbitrary units) | 760.33 (471.61–940.72) | 624.02 (460.94–866.76) | 822.93 (623.98–1,002.69) | 1,003.02 (699.24–1,310.61) | 52.80 (28.99–138.02) |
| Maximum relative enhancement (%) | 117.32 (84.94–148.99) | 190.03 (149.84–263.73) | 183.86 (139.74–236.02) | 242.62 (152.6–321.89) | 10.23 (5.04–34.55) |
| Time to peak SI (s) | 44.84 (34.8–61.86) | 70.50 (50.73–120.08) | 71.12 (44.78–93.19) | 96.64 (41.41–123.72) | 115.64 (51.78–147) |
| Uptake rate (s−1) | 59.93 (40.86–90.04) | 43.77 (20.31–84.04) | 66.35 (22.84–100.99) | 64.95 (29.27–90.33) | 7.75 (3.93–13.04) |
| Washout rate (s−1) | 21.14 (6.62–50.25) | 7.23 (0.80–19.89) | 6.06 (2.03–11.48) | 6.87 (0–28.83) | 1.04 (0.06–1.87) |
| Brevity of enhancement (s) | 40.32 (27.62–126.96) | 57.61 (6.90–146.47) | 75.11 (10.36–142.95) | 85.14 (0–159.78) | 99.15 (10.36–150.91) |
| Area under the time-intensity curve (arbitrary units) | 59,040 (17,016–129,607) | 53,236 (20,645–123,915) | 78,416 (25,652–151,046) | 93,451 (24,045–1,758,233) | 352 (21–14,992) |
| Area of the ROI (mm2) | 69.51 (58.89–89.56) | 48.88 (41.66–84.35) | 20.33 (16.77–33.56) | 14.47 (6.50–21.29) | 42.19 (21.58–54.95) |
Data were collected for 12 cats, but morphological images revealed that the shape and structure of the kidneys were abnormal in 2 cats; therefore, data for these 2 cats were excluded.
Relative enhancement was a measure of signal enhancement of a pixel in the PW-MRI scan, compared with signal enhancement for that pixel in an MRI scan obtained prior to administration of contrast medium. Maximum enhancement was the difference between initial intensity and peak intensity. Maximum relative enhancement was the maximum for all relative enhancements over all dynamics. Time to peak SI was the time from the start of the scan until maximum SI was detected. Uptake rate was the maximum slope between the time of onset of contrast medium inflow and time of peak intensity. Washout rate was the maximum slope between the time of peak intensity and time that the contrast medium was eliminated. Brevity of enhancement represented the time between the maximum uptake rate and maximum washout rate. Area under the time-intensity curve represented the sum of all intensities.
Median (range) values for ratios of selected PW-MRI variables for each of 4 ROIs for the 10 cats of Table 1.
| Variable* | Hepatic parenchyma | Splenic parenchyma | Renal cortex | Renal medulla |
|---|---|---|---|---|
| Relative enhancement | 3.32 (2.24–6.52) | 5.53 (4.12–11.87) | 6.12 (5.46–11.77) | 7.48 (5.22–14.99) |
| Maximum enhancement | 14.05 (3.85–28.23) | 12.81 (4.48–20.89) | 15.74 (5.09–27.92) | 18.02 (5.32–40.79) |
| Maximum relative enhancement | 10.78 (3.09–23.63) | 21.12 (4.34–32.89) | 18.42 (5.58–34.71) | 23.83 (5.95–59.08) |
| Time to peak | 0.39 (0.30–0.80) | 0.64 (0.44–1.13) | 0.60 (0.47–1.12) | 0.82 (0.68–1.17) |
| Uptake rate | 7.20 (3.25–17.90) | 5.20 (1.79–11.66) | 8.09 (3.60–15.56) | 8.14 (4.61–16.44) |
| Washout rate | 25.67 (6.30–218.5) | 8.55 (0.76–29.39) | 7.57 (2.32–37.29) | 8.81 (0–27.46) |
| Brevity of enhancement | 0.80 (0.28–2.67) | 0.94 (0.12–2.00) | 0.91 (0.36–2.21) | 0.92 (0–2.00) |
| Area under the time-intensity curve | 250.27 (3.67–2,880.43) | 258.67 (4.45–2,114.06) | 367.21 (5.53–3,066.14) | 446.31 (5.18–3,637.51) |
| Area of the ROI | 1.69 (0.71–3.69) | 1.21 (0.76–2.20) | 0.52 (0.33–1.20) | 0.37 (0.20–0.65) |
For each cat, ratios were calculated wherein each perfusion variable for a given ROI was divided by the corresponding variable for the epaxial muscle.
See Table 1 for remainder of key.
Representative T1-weighted PW-MRI images obtained in the transverse plane of the cranial aspect of the abdomen (A) and of the kidneys (B) of a cat. An ROI has been manually drawn on the hepatic parenchyma (blue circle), splenic parenchyma (green circle), epaxial musculature (purple circle), renal cortex (black circle), and renal medulla (red circle). Ventral is at the top of each image, and the right side of the cat is to the left of each image. Bar = 10 mm.
Citation: American Journal of Veterinary Research 80, 2; 10.2460/ajvr.80.2.159
The DW-MRI images of the liver of all 12 cats were evaluated. The images had limited spatial resolution. Qualitative evaluation of the ADC plot revealed that the liver of all cats was hyperintense, compared with the spleen, which was the most hypointense structure. The DWI-MRI images of kidneys of 10 cats were evaluated, and 2 cats with abnormalities in the morphological images were excluded. In these 10 cats, the renal cortex SI was extremely similar to the SI of the liver. The medulla was visible as a hyperintense band, compared with the cortex of every kidney of every cat, but the renal medulla was not visible on every slice.
Mean ± SD size of the ROI was 50.1 ± 11.4 mm2 for the hepatic parenchyma, 46.7 ± 11.9 mm2 for the splenic parenchyma, 28.1 ± 4.4 mm2 for the renal cortex, and 17.5 ± 3.2 mm2 for the renal medulla. There was no significant difference among the ROIs for each structure (ie, among the ROIs of the liver, ROIs of the spleen, ROIs of the renal cortices, and ROIs of the renal medullae); thus, the mean value for each structure was calculated. There was no significant difference between the ROIs for the right and left kidneys; thus, a mean value for both kidneys was calculated.
Median ADC of the hepatic parenchyma was 1.38 × 10−3 mm2/s (range, 1.15 × 10−3 to 1.54 × 10−3 mm2/s) and of the splenic parenchyma was 0.71 × 10−3 mm2/s (range, 0.66 × 10−3 to 0.84 × 10−3 mm2/s; Figure 4). Mean ± SD normalized ADC for the liver was 1.86 ± 0.18.
Representative DW-MRI images obtained in the transverse plane of the hepatic parenchyma (A) and splenic and renal parenchyma (B) of a healthy adult male cat. An ROI has been manually drawn on the hepatic parenchyma in the right cranial aspect of the liver (purple circle), splenic parenchyma (white circle), renal cortex (green circle), and renal medulla (red circle). Notice the limited spatial resolution. Ventral is at the top of each image, and the right side of the cat is to the left of the image. Bar = 10 mm.
Citation: American Journal of Veterinary Research 80, 2; 10.2460/ajvr.80.2.159
The DW-MRI images of the kidneys of 10 cats were evaluated. Median ADC was 1.65 × 10−3 mm2/s (range, 1.29 × 10−3 to 1.94 × 10−3 mm2/s) for the renal cortex and 1.93 × 10−3 mm2/s (range, 1.42 × 10−3 to 2.07 × 10−3 mm2/s) for the renal medulla (Figure 4). There was a significant (P = 0.03) difference between the ADC of the renal cortex and the ADC of the renal medulla.
Discussion
To our knowledge, the diagnostic value of morphological and functional MRI for parenchymatous organs of the feline abdomen has not been investigated. The study reported here represented the first information on functional MRI applied to the feline abdomen.
In human medicine, MRI is widely used for comprehensive examination of the liver, providing information on the presence of fat, iron, and fibrosis; neoplastic processes; and portal hypertension.7 Similarly, MRI is the only modality that combines noninvasive evaluation of the structure, hemodynamics, and oxygenation of the kidneys.8 Special interest has also been directed at evaluating kidneys for use in transplantation to human patients.9
Organ perfusion can be assessed by monitoring the uptake and washout of gadolinium-based contrast agents by the use of high temporal resolution.7 In human medicine, PW-MRI is used as an ancillary method for grading cirrho-sis10 and characterizing diffuse11 and focal12 liver lesions. Perfusion evaluation of the kidneys is also commonly performed because this technique can provide an estimation of the glomerular filtration rate and enable evaluation of vascular abnormalities, parenchymal diseases, and allografts.13
In veterinary medicine, most of the studies that involved PW-MRI conducted in clinical settings concern intracranial pathological conditions. The PW-MRI variables of parenchymatous organs in healthy dogs have been reported.14 In the present study, the hepatic peak was the earliest peak in 10 cats. This was expected because of the dual hepatic blood supply. In 2 cats, the hepatic peak was concurrent with the renal peak. That could be explained on the basis of the technique because scanning consisted of consecutive scans; thus, the hepatic peak could have potentially been missed. The PW-MRI SI of the hepatic peak was usually (10/12 cats) lower than the SI of the splenic peak. That was influenced by the duration of the scan because the splenic peak tended to increase over time. In accordance with information described previously,5 both the renal cortex and renal medulla in the present study had marked contrast enhancement, with the SI of the medulla typically exceeding that of the cortex over time in 8 of 10 cats. In 2 cats, the SI of the medulla was slightly lower than the SI of the cortex. It is possible that with a longer scanning time, the SI of the medulla would have exceeded the SI of the cortex.
Use of DW-MRI images allows measurement of the random motion of water molecules in biological tissues, which is most commonly quantified with the ADC.9 The movement of water within biological tissues is influenced by interactions among tissue compartments and is categorized as intravascular, intracellular, or extracellular.15 Moreover, water molecular diffusion is influenced by perfusion in the capillary network. It is important to know that ADC values are influenced by, among other factors, the strength of the gradient applied (which is expressed as b values). Pathological changes in tissue structure often reflect a change in the motion of water molecules. In the liver in particular, ADC values are used in human medicine to aid in the diagnosis and grading of hepatic fibrosis16 (and are lower for a healthy liver) and the differentiation of benign from malignant hepatic lesions.17 The kidneys are of particular interest for evaluation by means of ADC measurements because of the high blood flow and water transport functions.18 At low b values, factors other than passive diffusion (eg, perfusion attributable to blood flow and tubular flow) contribute greatly to ADC values for the kidneys19 such that b values > 400 s/mm2 are recommended for obtaining diffusion measurements.13 Considering the sensitivity of diffusion to flow changes, ADC of the kidneys is also influenced by diuretic treatments because of changes in vascular flow, tubular dilation, water resorption, and intratubular flow.9 In human medicine, differences have been described in normal kidneys and in focal9 and diffuse18 renal diseases, with ADC values gradually decreasing with increasing severity of the renal pathological changes.20 In veterinary medicine, the clinical use of DW-MRI is typically reserved for investigation of intracranial lesions in dogs21 and cats.22
The b values used in the present study were selected on the basis of published information for humans10,13; however, there is no consensus on the optimal parameters for the liver or kidneys. The b values used for DW-MRI typically do not exceed 1,000 s/mm2, and b values < 1,000 but > 500 s/mm2 are typically used for hepatic imaging. In the present study, b values were adjusted to obtain images with acceptable spatial resolution.
The ADC values are influenced by a number of factors involving patients, hardware, field strength, MRI unit, coils,23 acquisition parameters,24 location of the ROI where the ADC is calculated,25 and technical factors (breath-holding, free-breathing, or respiratory- or navigator-triggered events).25 In human medicine, a method for normalizing the ADC for hepatic tissue has been proposed in which the ADC of hepatic tissue is divided by the ADC of splenic tissue.26 The spleen is considered a reliable internal standard,26 even in the presence of hepatic disease, and is usually in the field of view for scans of the liver.27 Normalized ADC values for the liver with the spleen used as a reference organ reportedly are superior to absolute ADC values for distinguishing among degrees of liver cirrhosis.27 Most of the literature for human medicine regarding the ADC of the spleen concerns its association with the ADC of the liver. Diagnostic applications have been reported for differentiation of intrapancreatic accessory spleen from small pancreatic tumors28,29 and improved differentiation of malignant from benign splenic lesions30 and for patients with chronic hepatopathies.31 Changes in splenic DW-MRI have been used to stage liver fibrosis in miniature pigs.32 Absolute and normalized hepatic ADC values for healthy dogs have been described.14 Hepatic ADC in dogs and cats should not be directly compared because of the difference in b values of the scanning protocols for the 2 species. Despite differences of the mean ± SD ADC of the hepatic parenchyma between dogs (0.84 × 10−3 ± 0.12 × 10−3 mm2/s) and cats (1.36 × 10−3 ± 0.12 × 10−3 mm2/s), the normalized mean ADC in both species is similar (1.8 ± 0.4 in dogs and 1.86 ± 0.18 in cats).
The ADC values of the renal cortex reported in human medicine range between 2.00 × 10−3 mm2/s and 2.63 × 10−3 mm2/s.9,33–36 In 1 study18 of healthy individuals, ADC values were 2.55 × 10−3 mm2/s in the cortex and 2.84 × 10−3 mm2/s in the medulla. Results of the study reported here were similar in that the ADC of the medulla was higher than that of the cortex. Despite the fact there is greater blood flow in the renal cortex, the medulla reportedly has more water content per unit of tissue than the cortex. Therefore, it appears likely that the ADC reflects the difference in water content between the cortex and medulla.18 However, the opposite result has been reported in other studies,9,35 with a lower ADC in the medulla than in the cortex. This difference in SI between the renal cortex and renal medulla has been determined by use of 1.5-T and 3-T MRI units. Other authors37,38 reported that the medulla is not distinguishable from the cortex, but no attempt was made to separately evaluate the 2 regions. However, both of those studies37,38 were conducted with a 1.5-T unit. Respective b values have ranged from 0 to 1,000 s/mm2 and differed among studies. Therefore, we conclude that field strength is not the only factor that determines image resolution, because the choice of b values and other scan parameters can influence the ability to differentiate the cortex from the medulla.
In human medicine, ADC values of the renal cortex have been reported39,40 (1.63 × 10−3 ± 0.14 × 10−3 mm2/s [with b values between 50 and 1,300 s/mm] and 1.68 × 10−3 ± 0.15 × 10−3 mm2/s [with b values of 30, 900, and 1,200 s/mm2]) that are similar to the values for the cats of the present study. In addition, ADC values similar to those for the present study have been reported41 for rats, with an ADC of the cortex of 1.63 × 10−3 mm2/s and of the medulla of 1.72 × 10−3 mm2/s, with b values ranging from 0 to 1,000 s/mm2.
New technology has enabled DW-MRI images to be obtained over a fairly brief scan time (between 2 and 4 minutes of sequence length). That amount of time usually is acceptable for clinical settings. The major advantage of DW-MRI is that there is no need for the use of gadolinium-based contrast medium, which reportedly has been associated with nephrogenic systemic fibrosis in humans.42
However, DW-MRI images of the liver frequently contain motion artifact caused by respiration and motion of adjacent organs such as the heart. This may influence the ADC values obtained for different regions of the liver.25 We decided to use a free-breathing technique for the present study because of the shallow movements of the cats during respiration, which did not allow us to obtain a triggered sequence.
Another important source of variation for ADC is the location of the ROI within the organ parenchyma. In the present study, ADC was measured in the liver and renal cortex in areas of homogeneous SI. However, considering that the renal medulla was not visible in all images, a certain degree of inaccuracy must be assumed. Equipment differences (eg, differences in magnetic field strength or coils) also can contribute to difficulties in standardization of ADC values.23
The anesthetic protocol used is critical for perfusion evaluations because several anesthetic drugs and the use of artificial ventilation affect the cardiovascular system. Furthermore, blood pressure may not be measurable in some clinical settings. Nevertheless, we used the drug combination with the least cardiovascular-depressing effects that still allowed us to handle the research cats with the least stress possible.43 Alfaxalone and isoflurane were chosen because they had minimal negative cardiovascular effects.44,45
Limitations of the present study included a small study population that was homogeneous in terms of sex, breed, and body weight and did not accurately represent the potential population of clinical patients. No invasive procedures (eg, fine-needle aspiration or tissue biopsy) were conducted on the animals to enable us to rule out pathological conditions. Organs and structures were considered normal on the basis of the morphological images and a lack of biochemical abnormalities, despite a mildly irregular renal surface in 3 cats, which was considered to be a minor change. Subclinical pathological conditions of the liver, spleen, and kidneys cannot be excluded. Other abdominal organs (eg, pancreas and adrenal glands) were occasionally visible in the late postcontrast images, but the protocol was not optimized for evaluation of those organs.
Another limitation of the study was the manual injection of contrast medium. Use of a pump for injection decreases the variability of some of the variables relative to perfusion. However, quantitative analysis of the shape of a bolus does not differ significantly between manual and power-injector administration.46 Moreover, approximately 62.1% of the magnetic resonance angiography procedures for humans in Germany and 27.3% of the procedures for humans in the United States are performed without a power injector.46 Considering the extremely small volume of contrast medium administered to the cats of the present study, it would be reasonable to assume that any influence of the velocity of injection was limited. Higher injection rates are critical when synchronization of the bolus peak and image acquisition is required. In the study reported here, images of structures and organs were obtained from before the injection to minutes after the end of the injection. The injections were performed by trained personnel. Thus, even though a certain degree of variability should be assumed for some of the reported variables (eg, time to peak, uptake and washout rates, and maximal enhancement), we considered the generated data to be acceptable for analysis.
To our knowledge, functional MRI techniques have not been described or investigated for use in the diagnosis of hepatic and renal disease of cats in clinical settings. The present study provided a description of the use of PW-MRI and DW-MRI to evaluate the liver, spleen, and kidneys of healthy adult male cats. The reported data provided baseline information. Additional studies involving clinical patients are necessary to validate and refine the findings of the present study and to investigate the potential clinical applications of PW-MRI and DW-MRI for assessment of the abdominal organs of cats.
Acknowledgments
The authors declare that there were no conflicts of interest.
ABBREVIATIONS
| ADC | Apparent diffusion coefficient |
| ASA | American Society of Anesthesiologists |
| DW-MRI | Diffusion-weighted MRI |
| PW-MRI | Perfusion-weighted MRI |
| ROI | Region of interest |
| SI | Signal intensity |
Footnotes
Philips Ingenia scanner, Philips AG, Zurich, Switzerland.
dStream Torso, coil solution, 32 channels, Philips AG, Zurich, Switzerland.
Omniscan, 0.3 mmol/kg, GE Healthcare AG, Glattbrugg, Switzerland.
Philips Intellispace Ingenia (2016–09–12), Philips Medical Systems, Best, Netherlands.
SPSS statistics, version 21.0.0.0, 64-bit edition, IBM Corp, Chicago, Ill.
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