• View in gallery

    Representative transverse DW-MRI image of the prostate gland of a healthy sexually intact adult Beagle. The image was obtained at the level of the central aspect of the prostate gland. The ROIs have been manually drawn in the ventral central (white circles) and dorsal peripheral (black circles) regions of the right and left lobes of the prostate gland. Notice the limited spatial resolution. Dorsal is at the top of the image, and the right side of the dog is to the left side of the image. Bar = 10 mm.

  • View in gallery

    Representative transverse T1-weighted PW-MRI image of the cranial aspect of the prostate gland of a healthy sexually intact adult Beagle. The ROIs have been manually drawn on the parenchyma of the ventral (white circles) and dorsal (black circles) aspects of the right and left lobes of the prostate gland. In addition, 2 ROIs are indicated in the gluteal musculature of the right and left sides (dashed white circles). However, for the data analysis, the ROIs for the gluteal musculature were manually drawn on images approximately 2 or 3 slices more caudally. Dorsal is at the top of the image, and the right side of the dog is to the left side of the image. Bar = 10 mm.

  • View in gallery

    Transverse T2-weighted (A), T1-weighted precontrast (B), and T1-weighted postcontrast (C) images with fat suppression of the prostate gland of a representative healthy sexually intact adult Beagle. Dorsal is at the top of the image, and the right side of the dog is to the left side of the image. Bar = 10 mm.

  • View in gallery

    Time-intensity curves for a representative healthy sexually intact adult Beagle. Curves depict values for the ROIs drawn in the parenchyma of the dorsal aspect of the right lobe of the prostate gland (solid black line), parenchyma of the ventral aspect of the right lobe of the prostate gland (solid gray line), parenchyma of the dorsal aspect of the left lobe of the prostate gland (dashed black line), parenchyma of the ventral aspect of the left lobe of the prostate gland (dashed gray line), and gluteal musculature on the right (dotted-and-dashed black line) and left (dotted-and-dashed gray line) sides. Time after initiation represents the time after starting image acquisition.

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Diffusion-weighted and perfusion-weighted magnetic resonance imaging of the prostate gland of healthy adult dogs

Florian Willmitzer Dr Med Vet1, Francesca Del Chicca Dr Med Vet, PhD1, Patrick R. Kircher Dr Med Vet, PhD1, Adriano Wang-Leandro DVM, PhD1, Peter W. Kronen Dr Med Vet2, Dagmar Verdino Dr Med Vet2, Daniel Rüfenacht Dr Med3, Beat Porcellini Dr Med4, and Henning Richter Dr Med Vet, PhD1,2,3,4
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  • 1 1Clinic for Diagnostic Imaging, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland.
  • | 2 2Veterinary Anaesthesia Services-International, Zürcherstrasse 39, 8400 Winterthur, Switzerland.
  • | 3 3Department of Neuroradiology, Clinic Hirslanden, Witellikerstrasse 40, 8032 Zurich, Switzerland.
  • | 4 4Department of Abdominal and Urogenital Radiology, Clinic Hirslanden, Witellikerstrasse 40, 8032 Zurich, Switzerland.

Abstract

OBJECTIVE

To describe diffusion and perfusion characteristics of the prostate gland of healthy sexually intact adult dogs as determined by use of diffusion-weighted and perfusion-weighted MRI.

ANIMALS

12 healthy sexually intact adult Beagles.

PROCEDURES

Ultrasonography of the prostate gland was performed. Subsequently, each dog was anesthetized, and morphological, diffusion-weighted, and perfusion-weighted MRI of the caudal aspect of the abdomen was performed. The apparent diffusion coefficient was calculated for the prostate gland parenchyma in diffusion-weighted MRI images in the central ventral and peripheral dorsal areas. Perfusion variables were examined in multiple regions of interest (ROIs) in the ventral and dorsal areas of the prostate gland and in the gluteal musculature. Signal intensity was determined, and a time-intensity curve was generated for each ROI.

RESULTS

Results of ultrasonographic examination of the prostate gland revealed no abnormalities for any dog. Median apparent diffusion coefficient of the prostate gland was 1.51 × 10−3 mm2/s (range, 1.04 × 10−3 mm2/s to 1.86 × 10−3 mm2/s). Perfusion-weighted MRI variables for the ROIs differed between the prostate gland parenchyma and gluteal musculature.

CONCLUSIONS AND CLINICAL RELEVANCE

Results provided baseline information about diffusion and perfusion characteristics of the prostate gland in healthy sexually intact adult dogs. Additional studies with dogs of various ages and breeds, with and without abnormalities of the prostate gland, will be necessary to validate these findings and investigate clinical applications.

Abstract

OBJECTIVE

To describe diffusion and perfusion characteristics of the prostate gland of healthy sexually intact adult dogs as determined by use of diffusion-weighted and perfusion-weighted MRI.

ANIMALS

12 healthy sexually intact adult Beagles.

PROCEDURES

Ultrasonography of the prostate gland was performed. Subsequently, each dog was anesthetized, and morphological, diffusion-weighted, and perfusion-weighted MRI of the caudal aspect of the abdomen was performed. The apparent diffusion coefficient was calculated for the prostate gland parenchyma in diffusion-weighted MRI images in the central ventral and peripheral dorsal areas. Perfusion variables were examined in multiple regions of interest (ROIs) in the ventral and dorsal areas of the prostate gland and in the gluteal musculature. Signal intensity was determined, and a time-intensity curve was generated for each ROI.

RESULTS

Results of ultrasonographic examination of the prostate gland revealed no abnormalities for any dog. Median apparent diffusion coefficient of the prostate gland was 1.51 × 10−3 mm2/s (range, 1.04 × 10−3 mm2/s to 1.86 × 10−3 mm2/s). Perfusion-weighted MRI variables for the ROIs differed between the prostate gland parenchyma and gluteal musculature.

CONCLUSIONS AND CLINICAL RELEVANCE

Results provided baseline information about diffusion and perfusion characteristics of the prostate gland in healthy sexually intact adult dogs. Additional studies with dogs of various ages and breeds, with and without abnormalities of the prostate gland, will be necessary to validate these findings and investigate clinical applications.

Diseases of the prostate gland are common in dogs, accounting for up to 10% of the pathological conditions in sexually intact male dogs examined by veterinary surgeons.1 Among these, malignant neoplasias are rare, with estimated prevalences of prostate gland carcinoma of 0.2% and 0.6%.2 Because cancer of the prostate gland is highly aggressive, with macroscopic metastasis detected at necropsy in 80% of affected animals,3 an early diagnosis is crucial for the management of patients. In contrast to the United States, where most of the dogs are neutered, the percentage of sexually intact animals in Europe can be highly variable among countries. In some countries, most of the animals are gonadally intact4 and thus more prone to pathological conditions of the prostate gland. Moreover, dogs are the only animals other than humans that naturally develop prostate gland cancer; therefore, dogs can serve an important role for the study of prostate gland disease of humans.5 Thus, investigation of the prostate gland has been a focus of recent scientific studies.

A noninvasive method to diagnose prostate gland diseases in dogs relies on clinical examination, laboratory analysis, and diagnostic imaging. Radiographic and ultrasonographic findings are not pathognomonic for any prostate gland diseases.1 Contrast-enhanced ultrasonography has been described as an additional aid for use in differentiating benign from malignant prostate gland lesions,6 but this technique is not routinely used in veterinary medicine.

The incidence of prostate gland cancer is much higher in human medicine than in veterinary medicine, and the incidence of cancer progressively increases with age.7 Means of diagnosis with high specificity and sensitivity and that also can serve as adequate screening methods have been evaluated. Use of MRI to provide a combination of morphological and functional images has become the standard method for investigation of pathological conditions of the prostate gland.7 Morphological imaging (typically T2-weighted images and T1-weighted precontrast and postcontrast images) is commonly used for detection and localization of possible lesions, identification of changes after biopsy, and monitoring of disease. In addition, functional MRI (PW-MRI, DW-MRI, and spectroscopic imaging) have been recommended as potential complements.8 Perfusion-weighted MRI (or dynamic contrast-enhanced MRI) is widely used as a tool to discriminate between benign and malignant lesions9 and for accurate localization of tumors (primarily in the peripheral zone of the prostate gland), local staging of tumors, and detection of tumor recurrence.10

In human medicine, DW-MRI with corresponding quantification of the ADC value has been used to discriminate malignant neoplasia from normal prostate gland tissue or benign processes.11,12 Values for ADC correlate with the score of aggressiveness of prostate gland tumors.13,14

The availability of cross-sectional imaging modalities is increasing in veterinary medicine, and the use of such modalities to assess the prostate gland is garnering interest. There is a paucity of reports and lack of detailed description of the prostate gland and pathological conditions of the prostate gland. To the authors' knowledge, results of functional MRI of the prostate gland of clinically normal dogs have not been reported. Therefore, the objective of the study reported here was to assess the feasibility for use of PW-MRI and DW-MRI in the evaluation of the prostate gland of dogs in a clinical setting and to describe the perfusion pattern as well as the DW-MRI characteristics of the prostate gland in a sample of healthy sexually intact adult dogs. These data would provide baseline information for use in evaluation of pathological conditions of the prostate gland of dogs.

Materials and Methods

Animals

Twelve purpose-bred adult Beagles were enrolled in the study. All were sexually intact males with a median age of 89 months (range, 37 to 118 months) and median body weight of 14.8 kg (range, 11 to 18.4 kg). All dogs were considered healthy on the basis of results of a physical examination (including per rectal palpation) and hematologic analysis, and they were assigned American Society of Anesthesiologists class 1 status. All study procedures were reviewed and approved by the Cantonal Veterinary Office of Zurich (license No. ZH026/16) and performed in accordance with the Animal Welfare Act of Switzerland.

Ultrasonographic examination

Ultrasonographic examinationa of the prostate gland of each dog was performed; 1 investigator (FW), who was a board-certified veterinary radiologist with 13 years of experience, performed all ultrasonographic examinations. Dogs were awake and gently restrained. The prostate gland was scanned in longitudinal and transverse planes with a microconvex transducerb and a linear transducer.c Gray-scale B-mode images were recorded and analyzed. A prostate gland was considered ultrasonographically normal when it was of medium echogenicity, was homogeneous, had a fine to medium-coarse echotexture, and had smooth margins and symmetric lobes.15

Anesthesia and instrumentation of dogs

Seven to 10 days after ultrasonography was performed, dogs were anesthetized, and the prostate gland of each dog was evaluated by use of MRI. Food was withheld from each dog beginning the evening before the MRI examination. Dogs were premedicated with methadone (0.2 mg/kg, IM), and a catheter was aseptically placed in a cephalic vein. Oxygen was administered via a face mask for 3 to 5 minutes, and anesthesia then was induced with midazolam (0.1 mg/kg, IV) and propofol (2.2 to 3.3 mg/kg, IV, to effect). The trachea of each dog was intubated with a cuffed endotracheal tube, which was connected to a circle rebreathing system. Anesthesia was maintained with sevoflurane administered in an oxygen-air mixture (1 part oxygen to 2 parts air); gas flow rate was 50 mL/kg/min. Each dog was mechanically ventilated with a volume-controlled ventilator set at a tidal volume of 10 mL/kg and a rate of 15 breaths/min to maintain an end-tidal partial pressure of CO2 of 35 to 45 mm Hg. Infusion of lactated Ringer solution (5 mL/kg/h, IV) was initiated and maintained throughout the procedure. Cardiovascular and respiratory variables were measured continuously and recorded by a multiparameter monitor that included an MRI-compatible wireless respiratory sensor, vectorcardiography unit, and pulse oximeter (the probe was placed on the tongue of each dog) as well as a spirometry unit to monitor airway pressures and volumes. Inspired and expired sevoflurane concentrations were continuously measured. Mean arterial blood pressure was monitored by use of a noninvasive, oscillometric method; mean arterial blood pressure was maintained between 70 and 85 mm Hg by adjusting the inspired fraction of sevoflurane.

MRI

Each dog was positioned in sternal recumbency, and images were obtained with a 3-T MRI system.d An integrated built-in posterior coil was used, and 2 flex coilse were placed overlapping at approximately the level of the lumbosacral junction. Morphological imaging included T2-weighted images of the prostate gland in the transverse plane (turbo spin echo; repetition time, 2.972 milliseconds; echo time, 110 milliseconds; flip angle, 90°; field of view, 190/101/62 mm; voxel size, 0.60/0.60/2.50 mm; slice thickness, 2.5 mm; and slice gap, 0 mm) and T1-weighted images in the transverse plane (fast field echo; repetition time, 3.6 milliseconds; echo time 1, 1.31 milliseconds; echo time 2, 2.3 milliseconds; flip angle, 10°; field of view, 100/117/100 mm; voxel size, 0.65/0.65/2.0 mm; slice thickness, 2 mm; and slice gap, −1.0 mm) with fat suppression. Functional sequences included DW-MRI (3b imaging performance sensitivity encoding; repetition time, 2.896 milliseconds; echo time, 71 milliseconds; flip angle, 90°; field of view, 180/180/51 mm; voxel size, 1.5/1.84/3.00 mm; slice thickness, 3 mm; slice gap, 0 mm; number of directions, 4; and number of b values, 3 [0, 500, and 1,000] obtained in the transverse plane). Then, 4 mL of contrast mediumf was administered IV (injection rate, 2 mL/s) with an MRI-compatible pump injector, which was followed by injection of 15 mL of saline (0.9% NaCl) solution. A bolus-tracked T1-PW-MRI sequence was obtained in the transverse plane over the caudal aspect of the abdomen (multitransmit-enhanced high-resolution isotropic volume examination, dynamic parallel imaging performance sensitivity encoding, T1 turbo field echo; repetition time, 5.0 milliseconds; echo time, 2.5 milliseconds; flip angle, 15°; field of view, 181/200/60 mm; voxel size, 0.95/1.13/3.00 mm; slice thickness, 3 mm; slice gap, −1.5 mm; and number of dynamics, 50). Injection of the contrast medium was started at the third dynamic. After the dynamic sequence was completed, a T1-weighted sequence with fat suppression was obtained in the transverse plane (fast field echo; repetition time, 5.4 milliseconds; echo time, 2.7 milliseconds; flip angle, 10°; field of view, 100/117/100 mm; voxel size, 0.65/0.65/2.0 mm; slice thickness, 2 mm; and slice gap, −1.0 mm).

Processing of MRI data

Processing of MRI data was conducted on an extended workstation.g Quantitative ADC maps were derived from the DW-MRI images. Twelve ROIs of similar size were manually drawn on the prostate gland parenchyma. On each lobe, 3 ROIs were drawn in the central ventral region of the prostate gland (1 each in the cranial, middle, and caudal aspect of the parenchyma) and 3 ROIs were drawn in the peripheral dorsal region of the prostate gland (1 each in the cranial, middle, and caudal aspects of the parenchyma; Figure 1). Care was used to avoid the inclusion of large blood vessels, the urethra, and the boundary of the prostate gland in the ROIs. The ADC was calculated for each ROI.

Figure 1—
Figure 1—

Representative transverse DW-MRI image of the prostate gland of a healthy sexually intact adult Beagle. The image was obtained at the level of the central aspect of the prostate gland. The ROIs have been manually drawn in the ventral central (white circles) and dorsal peripheral (black circles) regions of the right and left lobes of the prostate gland. Notice the limited spatial resolution. Dorsal is at the top of the image, and the right side of the dog is to the left side of the image. Bar = 10 mm.

Citation: American Journal of Veterinary Research 80, 9; 10.2460/ajvr.80.9.832

On the PW-MRI images, 10 ROIs of similar size were manually drawn. On each lobe, 4 ROIs were drawn (1 each in the cranial ventral aspect of the parenchyma, caudal ventral aspect of the parenchyma, cranial dorsal aspect of the parenchyma, and caudal dorsal aspect of the parenchyma). Two additional ROIs were drawn in the gluteal musculature (right and left sides at approximately the level of the mid-length of the prostate gland). Each ROI was propagated through all images (Figure 2). Care was used to avoid the inclusion of large blood vessels, the urethra, and the boundary of the prostate gland in the ROIs.

Figure 2—
Figure 2—

Representative transverse T1-weighted PW-MRI image of the cranial aspect of the prostate gland of a healthy sexually intact adult Beagle. The ROIs have been manually drawn on the parenchyma of the ventral (white circles) and dorsal (black circles) aspects of the right and left lobes of the prostate gland. In addition, 2 ROIs are indicated in the gluteal musculature of the right and left sides (dashed white circles). However, for the data analysis, the ROIs for the gluteal musculature were manually drawn on images approximately 2 or 3 slices more caudally. Dorsal is at the top of the image, and the right side of the dog is to the left side of the image. Bar = 10 mm.

Citation: American Journal of Veterinary Research 80, 9; 10.2460/ajvr.80.9.832

For each ROI, the workstation software generated an SI-versus-time curve (ie, time-intensity curve). Other variables generated for each ROI by use of the PW-MRI images included relative enhancement, maximum enhancement, maximum relative enhancement, time to peak SI, wash-in rate, washout rate, brevity of enhancement, area under the time-intensity curve, and ROI size. Maximum enhancement was the difference between initial intensity and peak intensity. Relative enhancement was the measure of the signal enhancement of a pixel in a PW-MRI image, compared with the signal enhancement for that pixel in an MRI image 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 image acquisition until maximum attenuation. Wash-in 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 wash-in rate and the maximum washout rate. Area under the time-intensity curve represented the sum of all intensities. For each dog, ratios were calculated in which each perfusion variable for a given ROI was divided by the corresponding perfusion variable for the gluteal musculature.

Statistical analysis

Descriptive data were generated with a commercially available software program.h Results were reported as the median and range. Significant differences among the ROIs were assessed by use of the Wilcoxon test. Significance was set at P = 0.05.

Results

Ultrasonographic examination

For all dogs, the prostate gland was considered ultrasonographically normal on the basis of subjective evaluation of the size, shape, echogenicity, and echoarchitecture.

MRI

Evaluation of morphological images revealed that the prostate gland had a median height of 2.5 cm (range, 2.2 to 2.6 cm), median width of 3.5 cm (range, 3 to 3.8 cm), and median length of 3.5 cm (range, 2.9 to 3.9 cm). For all dogs, the prostate gland was well-defined by a hypointense capsule on T2-weighted images. For 5 dogs, the dorsal aspect of the gland was mildly flattened by the gas-containing colon; for 1 dog, the border was slightly irregular. Evaluation of T2-weighted images revealed that the prostate gland had a heterogeneous SI and was hyperintense, compared with results for the gluteal musculature. Within the gland, there were areas of hyperintense SI with a striated appearance and radial structure. These areas were accentuated dorsoperipherally in 5 dogs but were more uniform and evenly distributed in 7 dogs. Evaluation of T1-weighted fat-suppressed images revealed that SI of the prostate gland was homogeneous, and it was isointense, compared with results for the gluteal musculature in all dogs. Postcontrast T1-weighted images of 11 dogs were evaluated; images of 1 dog were excluded because of technical reasons. Median delay for acquisition of the postcontrast T1-weighted images was 287 seconds (range, 254 to 297 seconds). Evaluation of postcontrast and fat-suppressed T1-weighted images revealed that the capsule was hyperintense in all dogs. The parenchyma was mildly hyperintense, compared with the gluteal musculature, in 10 dogs and subjectively isointense in the other dog. For all dogs, the parenchyma was mildly heterogeneous, with hyperintense striations with a radial orientation. Subjectively, the amount of these striations was very mild for 5 dogs and more conspicuous for 6 dogs. For all 11 dogs, there was a hyperintense area around the urethra; subjectively, it was considered mild in 8 dogs and more accentuated in 3 dogs. For 1 dog, the intraprostatic portion of the urethra was mildly dilated. The SI of the prostate gland in the various sequences was determined (Figure 3).

Figure 3—
Figure 3—

Transverse T2-weighted (A), T1-weighted precontrast (B), and T1-weighted postcontrast (C) images with fat suppression of the prostate gland of a representative healthy sexually intact adult Beagle. Dorsal is at the top of the image, and the right side of the dog is to the left side of the image. Bar = 10 mm.

Citation: American Journal of Veterinary Research 80, 9; 10.2460/ajvr.80.9.832

The PW-MRI images of 11 dogs were analyzed; images of 1 dog were excluded because of technical reasons. Duration of image acquisition for the dynamic PW-MRI was approximately 300 seconds. Median heart rate was 90 beats/min (range, 67 to 132 beats/min). Median size of the ROI drawn on the PW-MRI images was 22.31 mm2 (range, 14.89 to 30.04 mm2) for the prostate gland parenchyma and 57.43 mm2 (range, 39.21 to 115.4 mm2) for the gluteal musculature. There were no significant differences for the perfusion variables between the right and left lobes of the prostate gland. Similarly, there were no significant differences for the perfusion variables between the cranial and caudal regions of the parenchyma. However, maximum enhancement and area under the time-intensity curve differed significantly (P = 0.001) between the ventral and dorsal regions of the prostate gland. Mean values of the ROIs for the right and left sides of the gluteal musculature were calculated. The PW-MRI variables for the ventral and dorsal regions of the prostate gland, the entire prostate gland, and the gluteal musculature and the ratio for the value for the prostate gland divided by the corresponding value for the gluteal musculature were summarized (Table 1). Time-intensity curves, which corresponded to the evaluated ROIs, were created (Figure 4).

Figure 4—
Figure 4—

Time-intensity curves for a representative healthy sexually intact adult Beagle. Curves depict values for the ROIs drawn in the parenchyma of the dorsal aspect of the right lobe of the prostate gland (solid black line), parenchyma of the ventral aspect of the right lobe of the prostate gland (solid gray line), parenchyma of the dorsal aspect of the left lobe of the prostate gland (dashed black line), parenchyma of the ventral aspect of the left lobe of the prostate gland (dashed gray line), and gluteal musculature on the right (dotted-and-dashed black line) and left (dotted-and-dashed gray line) sides. Time after initiation represents the time after starting image acquisition.

Citation: American Journal of Veterinary Research 80, 9; 10.2460/ajvr.80.9.832

Table 1—

Median (range) values for selected PW-MRI variables for the parenchyma in the ventral and dorsal areas of the prostate gland and for the gluteal musculature of I2 healthy sexually intact adult Beagles.

Prostate gland parenchyma  
VariableVentral areaDorsal areaMean overallGluteal musculatureRatio of prostate gland parenchyma to gluteal musculature
Relative enhancement (%)125.70 (100.13–195.73)108.96 (87.74–215.26)119.88 (102.0–88.54)35.77 (16.92–57.72)4.43 (2.11–7.38)
Maximum enhancement (au)72.39 (56.36–113.55)a66.17 (44.25–97.52)b68.65 (50.30–105.53)11.96 (7.22–26.74)5.42 (2.01–9.49)
Maximum relative enhancement (%)177.27 (138.89–556.06)171.18 (115.00–256.44)174.29 (126.95–364.97)26.47 (11.08–58.77)7.12 (2.47–13.38)
Time to peak S1 (s)59.54 (34.40–142.85)57.99 (46.63–144.40)58.76 (40.51–143.63)213.81 (71.68–284.92)0.32 (0.23–0.65)
Wash-in rate (s−1)6.89 (5.15–9.75)6.08 (3.75–8.85)6.34 (4.60–9.30)1.25 (1.02–2.35)4.94 (1.95–7.70)
Washout rate (s−1)2.10 (1.37–3.00)1.82 (1.35–2.29)2.00 (1.36–2.78)0.83 (0.06–1.33)2.30 (1.60–33.67)
Brevity of enhancement (s)157.74 (58.03–249.87)127.11 (60.61–247.44)142.42 (71.01–202.45)106.40 (43.52–190.10)1.09 (0.70–3.21)
Area under the time-intensity curve (au)15,794 (10,630–21,900)a12,516 (8,715–19,596)b14,353 (9,673–20,748)1,710 (15–5,413)8.97 (1.79–967.63)
ROI area (mm2)22.40 (16.33–31.85)22.22 (13.45–28.96)22.31 (14.89–30.04)57.43 (39.21–115.40)0.41 (0.13–0.57)

Within a row, values with different superscript letters differ significantly (P = 0.001).

au = Arbitrary units.

Evaluation of the PW-MRI images of all dogs revealed that there was rapid enhancement of the parenchyma of the prostate gland (approx 40 seconds after the beginning of the sequence). Subsequently, the SI gradually and slowly decreased for the remaining 260 seconds of the sequence, with the SI at the end of the sequence lower than the peak SI. For 3 dogs, the curve was extremely flat and the decrease of SI extremely limited, with the SI at the end of the sequence only slightly lower than the peak SI. The muscular tissue had no clear peak of enhancement. For all dogs, the SI slowly increased and reached a plateau, which was maintained throughout image acquisition. The peak SI of the prostate gland was approximately 4.43 times the SI of the gluteal musculature.

The DW-MRI images of 11 dogs were analyzed; images of 1 dog were excluded because of poor quality. Duration of the DW-MRI sequence was approximately 120 seconds.

Qualitatively, SI of the prostate gland on the ADC maps was always high, and it was higher than that of the surrounding tissues and gluteal musculature. The SI was homogenous in 3 dogs, with an area of lower SI around only the ventral part of the intraprostatic portion of the urethra. The SI was mildly heterogeneous in 8 dogs, with ill-defined hyperintensities. These areas were more conspicuous in the parenchyma of the dorsal region in 6 dogs and were accentuated dorsally and peripherally in 2 other dogs. The hyperintensities were nearly symmetric in all dogs.

Median of the ADC values for all the ROIs was 1.51 × 10−3 mm2/s (range, 1.04 × 10−3 mm2/s to 1.86 × 10−3 mm2/s). Median size for all the ROIs was 18.25 mm2 (range, 9.25 to 43.5 mm2). The ADC values did not differ significantly (P = 0.326) when ROIs for the parenchyma of the prostate gland were grouped and compared between the right and left lobes. Similarly, ADC values of the parenchyma in the cranial, middle, and caudal aspects of the prostate gland did not differ significantly between regions (cranial vs middle, P = 0.12; cranial vs caudal, P = 0.248; and middle vs caudal, P = 0.556). The ADC value for the parenchyma in the central ventral region of the prostate gland differed significantly (P = 0.001) from the value for the parenchyma in the dorsal peripheral aspect of the gland. Median ADC of the ROIs for the parenchyma in the central ventral region of the prostate gland was 1.33 × 10−3 mm2/s (range, 0.9 × 10−3 mm2/s to 1.76 × 10−3 mm2/s), and median ADC of the ROIs for the parenchyma in the dorsal peripheral region of the prostate gland was 1.68 × 10−3 mm2/s (range, 1.17 × 10−3 mm2/s to 2.01 × 10−3 mm2/s). Median size of the ROIs in the parenchyma of the central ventral region of the prostate gland was 18.5 mm2 (range, 9.5 to 40.33 mm2), and median size of ROIs in the parenchyma of the dorsal peripheral region of the prostate gland was 23.5 mm2 (range, 12.67 to 37.33 mm2). No significant (P = 0.13) difference was detected in ROI size when they were grouped for the central ventral and dorsal peripheral regions of the prostate gland.

Discussion

Noninvasive methods for diagnosis of prostate gland diseases in dogs traditionally have relied on clinical signs and ultrasonographic exmination.16 Hyperplastic, inflammatory, and neoplastic pathological conditions of the prostate gland may have similar ultrasonographic appearances; therefore, there are no pathognomonic ultrasonographic findings for any prostate gland diseases.1 Invasive techniques (eg, ultrasound-guided fine needle aspiration or biopsy) are commonly used to further investigate pathological conditions of the prostate gland, but they are operator dependent, with agreement with the final histologic diagnosis between 75% and 80%.17 Examination of fine-needle aspiration samples failed to detect malignancy in a dog with underlying benign prostatic hyperplasia,17 and it is not recommended in patients with transitional cell carcinoma because of the risk of seeding.15 Use of fine-needle aspiration (as well as biopsy) is questionable in patients with acute inflammation because acute peritonitis may develop as a consequence.18 Furthermore, ultrasonographic assessment of the structures surrounding the prostate gland and extending within the pelvic canal is limited by the pelvic bones.

One of the advantages of cross-sectional techniques is the possibility for evaluation of structures other than the prostate gland (eg, structures extending within the pelvic canal and the skeleton as potential sites of metastasis).1 Compared with CT, MRI has better contrast resolution, and the addition of functional imaging in human medicine enables further investigation of the nature of disease with good results, which has allowed the differentiation of prostate gland neoplasia from prostatitis and normal prostate gland parenchyma.11 Investigation of the prostate gland by use of MRI is not routinely conducted in veterinary medicine because of the need to anesthetize patients, high costs, and limited accessibility of equipment. However, there is growing interest in the use of MRI to evaluate the prostate gland of dogs, which is supported by the fact that dogs can be used to study prostate gland diseases that affect humans. Studies have focused on testing imaging options19 as well as interventional diagnostic and therapeutic interventions.20–23

Despite similarities of the pathophysiologic processes of prostate gland cancer between humans and dogs, there are some important differences in the anatomy of the prostate gland between the species. The prostate gland of humans is characterized by peripheral, transition, and central zones, each of which has characteristic histologic features and predisposition to certain diseases.24 However, the latter 2 zones cannot be resolved with diagnostic imaging and are often referred to as the central aspect of the gland.7 In contrast, the prostate gland of dogs lacks such zonal differences but has a uniform morphology along the longitudinal axis. Moreover, no preferential site for initiation of cancer of the prostate gland in dogs has been reported.25

In the present study, the SI and architecture of the prostate gland on the morphological images were similar to descriptions reported elsewhere.19 They were considered indicative of structurally normal prostate glands.

Diffusion-weighted images measure the random motion of water molecules in biological tissues and are most commonly quantified by use of the ADC. The ADC reflects the cellular status of physiologically normal and pathological tissues.7 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.7 There is no consensus regarding b values in human medicine.26 For this reason, standardization of ADC values is difficult, and various values have been reported. Moreover, different values have been reported for the peripheral zone and in the central aspect of normal prostate glands. For images obtained at 3 T, ADC values in the peripheral zone and the central aspect of the prostate gland of healthy men are 1.6 ± 0.25 × 10−3 mm2/s and 1.27 ± 0.14 × 10−3 mm2/s, respectively.27 In another study,26 ADC values were 1.5 × 10−3 mm2/s (range, 1.48 × 10−3 mm2/s to 1.55 × 10−3 mm2/s) for the transition zone and 1.71 × 10−3 mm2/s (range, 1.55 × 10−3 mm2/s to 1.83 × 10−3 mm2/s) for the peripheral zone, with a mean ADC of 1.67 × 10−3 mm2/s (range, 1.52 × 10−3 mm2/s to 1.80 × 10−3 mm2/s). Regardless of the choice of b values and field strength of the system, the peripheral zone has consistently higher ADC values. That is in agreement with data for the study reported here in which parenchyma in the central ventral region of the prostate gland had a median ADC of 1.33 × 10−3 mm2/s and parenchyma in the dorsal peripheral region had a median ADC of 1.68 × 10−3 mm2/s. In contrast with results for humans, no difference could be appreciated in the SI within the prostate gland of dogs in any of the sequences. Therefore, it would be reasonable to assume that differences in ADC values for the tissue's property were not resolved by evaluation of the images. This would be crucial in the evaluation of clinical patients and focal lesions because malignant lesions have lower ADC values (approx 20% to 40% lower) than benign processes or normal prostate gland tissue in humans.7

An advantage for DW-MRI images is that they can be obtained over a fairly brief scan time and without administration of contrast medium. They also allow evaluation of the entire prostate gland.

Perfusion-weighted MRI refers to imaging of tissue blood flow and microcirculation and reflects the perfused microvessel area, vessel permeability, and contrast leakage. Acquiring dynamic images allows evaluation of the temporal component, which enables assessment of the change in SI before, during, and after injection of a bolus of contrast medium.10 These changes are related to differences in microvascular characteristics between normal and malignant prostate gland tissues.28 The most important application of PW-MRI is for detection of neoplastic processes,29 localization and staging of prostatic carcinoma,30 and recurrence of disease.31 To the authors' knowledge, perfusion variables of the prostate gland of healthy dogs have not been investigated. Comparison of results for the prostate gland with results for the gluteal musculature was advantageous because the 2 tissues were in the same scanning field. Homogeneous enhancement was evident in the entire prostate gland, and enhancement of the prostate gland was much stronger (maximum relative enhancement was > 7 times as strong) than enhancement of the gluteal musculature.

The anesthetic protocol used is critical for perfusion evaluations because several anesthetic drugs affect the cardiovascular system. In the present study, mean arterial blood pressure was maintained within a fairly narrow range (70 to 85 mm Hg) to maintain perfusion in the tissues as constantly as possible. Anesthesia was induced with drugs that have no (midazolam) or only short-acting (propofol) effects on cardiovascular function.32 Anesthesia was maintained with sevoflurane, which preserves arterial blood flow fairly well.32

Limitations of the present study included a small number of dogs in the study that were homogeneous in terms of breed and body weight and that did not accurately represent the population of clinical patients with prostate gland disease. Also, it was determined that dogs did not have prostate gland disease on the basis of results of clinical examination, biochemical analysis, ultrasonographic examination, and morphological MRI. Ultrasonographic examination was used to rule out severe pathological changes because it represented the examination most commonly conducted in clinical settings. Assessment of the veterinary radiologist who performed the ultrasonographic examination was considered reliable for defining each prostate gland as ultrasonographically normal.

Beagles > 6 years old typically have histologic evidence of benign prostatic hyperplasia.33 Therefore, even if the prostate gland was morphologically normal, a certain degree of benign prostatic hyperplasia should be assumed for 7 of the 11 dogs of the present study. The influence of benign prostatic hyperplasia on variables for functional MRI images is unknown. In humans, benign prostatic hyperplasia results in nonhomogeneous SI on DW-MRI images and an increase in ADC values, compared with the ADC of the central zone in normal prostate glands.34 The low number of dogs in the present study did not allow us to make conclusions on the variation of ADC values on the basis of age.

To our knowledge, functional MRI techniques have not been described or investigated for use in the diagnosis of prostate gland diseases in veterinary species. The present study provided a description of the use of PW-MRI and DW-MRI for the evaluation of the prostate gland of healthy adult dogs. The MRI variables calculated provided baseline information about the diffusion and perfusion characteristics of the prostate gland in healthy sexually intact adult Beagles. Additional studies on dogs of various breeds and ages, with and without anomalies of the prostate gland, are necessary to validate and refine these findings and to investigate potential clinical applications and relevance of the use of PW-MRI and DW-MRI for assessment of the prostate gland of dogs.

Acknowledgments

Supported by the Marie-Louise von Muralt Foundation. The authors declare that there were no conflicts of interest.

ABBREVIATIONS

ADC

Apparent diffusion coefficient

DW-MRI

Diffusion-weighted MRI

PW-MRI

Perfusion-weighted MRI

ROI

Region of interest

SI

Signal intensity

Footnotes

a.

Aloka Alpha 10 ultrasound machine, Hitachi Medical Systems Europe Holding AG, Zug, Switzerland.

b.

7.5 MHz (5 to 10 MHz), Aloka UST-9120, Hitachi Aloka Medical America, Wallingford, Conn.

c.

12 MHz (5 to 13 MHz), Aloka UST-5412, Hitachi Aloka Medical America, Wallingford, Conn.

d.

Philips Ingenia scanner, Philips AG, Zurich, Switzerland.

e.

dStream Flex M, phased-array detection, 6 channels, Philips AG, Zurich, Switzerland.

f.

Omniscan, GE Healthcare AG, Glattbrugg, Switzerland.

g.

Philips Intellispace Ingenia, Philips Medical System, Best, Netherlands.

h.

SPSS Statistics, version 21.0.0.0, IBM Corp, Chicago, Ill.

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Contributor Notes

Dr. Willmitzer's present address is VET Zentrum AG, Riedäckerstrasse 7, 8422 Winterthur, Switzerland.

Drs. Willmitzer and Del Chicca contributed equally to the manuscript.

Address correspondence to Dr. Willmitzer (fwillmitzer@vetzentrum.ch).