• View in gallery

    Transverse spontaneous ventilation (SV; A) and positive-pressure breath-hold (PPBH; B) CT images of a healthy female mixed-breed dog showing 3 liver regions of interest adjacent to the diaphragm. The oval regions of interest were drawn on the liver adjacent to the right lateral border (dotted line), left diaphragmatic dome (dashed line), and left lateral border (solid line) at the level where the caudal vena cava completely enters into the liver (A; arrow).

  • View in gallery

    SV (A and C) and PPBH (B and D) transverse positron emission tomography (PET) images at the level of the left ventricle (A and B) and liver (C and D) in 5 healthy female mixed-breed dogs. SV PET images were acquired at 3 min/bed position; PPBH PET images at 1.5 min/bed position. Overall image quality and conspicuity of anatomic organs were superior in PPBH than in SV PET images without a difference in image noise. Superimposition of the liver (star) on the left ventricle was shown as the result of motion artifacts from SV (A). The thoracic wall, descending aorta (A, B, and D; black arrow), caudal vena cava (B; white arrow), and diaphragm (C and D; white arrowheads) were more clearly identifiable in PPBH PET images. L = Liver. V = Left ventricle. W = Thoracic wall.

  • View in gallery

    Transverse (A and B), dorsal (C and D), and sagittal (E and F) PET/CT images of the caudal thoracic region in SV (A, C, and E) and PPBH (B, D, and F) procedures in a healthy female mixed-breed dog. Compared with PPBH PET/CT images, SV PET/CT images showed a greater degree of misalignment of the left ventricle (white arrows) and liver (white arrowheads) in all planes and increased misalignment of gall bladder (white-outlined arrowhead) on the transverse plane. Superimposition of the left ventricle (star) on the liver was due to motion artifacts in SV PET.

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Positive-pressure breath-hold positron emission tomography/computed tomography is feasible for respiratory-induced artifact reduction in healthy dogs

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  • 1 Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, CA

Abstract

OBJECTIVE

To perform qualitative and quantitative analysis of positron emission tomography (PET)/CT images using spontaneous ventilation (SV) and positive-pressure breath-hold (PPBH) techniques in order to demonstrate the feasibility of PPBH PET/CT to decrease respiration-induced artifacts.

ANIMALS

5 healthy female mixed-breed dogs.

PROCEDURES

2-([18F]fluoro)-2-deoxy-D-glucose (was administered to each anesthetized dog. An SV PET/CT scan was performed from the head to the femur using 8 bed positions (3 min/bed) followed by a PPBH scan centered over the diaphragm with a single bed position (1.5 min/bed). PET image quality, the misalignment of organs between PET and CT images, and standardized uptake values (SUVs) of liver adjacent to diaphragm were compared between SV and PPBH.

RESULTS

Overall image quality and conspicuity of anatomic structures were superior in PPBH than in SV PET images. PPBH induced significantly less misalignment of the liver and diaphragm in all planes compared to SV. For the gall bladder, PPBH showed significantly less misalignment than SV only in the transverse plane. The maximum SUV in all of the liver areas was significantly higher with PPBH compared to SV. PPBH exhibited significantly higher mean SUV in the liver adjacent to the left diaphragmatic dome and left lateral border and higher minimum SUV only in the liver adjacent to the left diaphragmatic dome.

CLINICAL RELEVANCE

PPBH was demonstrated to be a feasible PET/CT protocol with higher PET image quality, less organ misalignment on fused PET/CT, and more accurate SUVs of the liver compared to SV PET/CT in healthy dogs.

Abstract

OBJECTIVE

To perform qualitative and quantitative analysis of positron emission tomography (PET)/CT images using spontaneous ventilation (SV) and positive-pressure breath-hold (PPBH) techniques in order to demonstrate the feasibility of PPBH PET/CT to decrease respiration-induced artifacts.

ANIMALS

5 healthy female mixed-breed dogs.

PROCEDURES

2-([18F]fluoro)-2-deoxy-D-glucose (was administered to each anesthetized dog. An SV PET/CT scan was performed from the head to the femur using 8 bed positions (3 min/bed) followed by a PPBH scan centered over the diaphragm with a single bed position (1.5 min/bed). PET image quality, the misalignment of organs between PET and CT images, and standardized uptake values (SUVs) of liver adjacent to diaphragm were compared between SV and PPBH.

RESULTS

Overall image quality and conspicuity of anatomic structures were superior in PPBH than in SV PET images. PPBH induced significantly less misalignment of the liver and diaphragm in all planes compared to SV. For the gall bladder, PPBH showed significantly less misalignment than SV only in the transverse plane. The maximum SUV in all of the liver areas was significantly higher with PPBH compared to SV. PPBH exhibited significantly higher mean SUV in the liver adjacent to the left diaphragmatic dome and left lateral border and higher minimum SUV only in the liver adjacent to the left diaphragmatic dome.

CLINICAL RELEVANCE

PPBH was demonstrated to be a feasible PET/CT protocol with higher PET image quality, less organ misalignment on fused PET/CT, and more accurate SUVs of the liver compared to SV PET/CT in healthy dogs.

Introduction

Positron emission tomography (PET)/CT is commonly used in human medicine and has gained importance recently in veterinary medicine, particularly in oncology, with regard to diagnosing and staging a variety of diseases and monitoring therapeutic response to radiotherapy and chemotherapy.1,2 The advantage of combined PET/CT imaging is that it provides simultaneous acquisition of morphological and functional information on the patient as well as a method of attenuation correction.3 Attenuation correction is used to normalize the standard uptake value (SUV) arising from different transmission of gamma rays through varying depths and types of tissues. CT-based attenuation correction for PET is more rapid than the traditional transmission attenuation correction, thus reducing the overall whole-body pet scanning time.4 However, CT-based attenuation correction for PET could cause artifacts that are not seen in the transmission-corrected PET images. Examples are artifacts due to respiratory motion, truncation, metallic implants, and CT contrast agents.5 Among all of these factors, respiratory motion during scanning is considered to be the most significant problem in CT-based attenuation correction.4,5

During PET acquisition, the patient breathes normally and the resultant images are comprised of PET images averaged over many breathing cycles. On the other hand, a CT scan is usually acquired at a particular phase point in the breathing cycle. As a consequence, respiratory motion from diaphragmatic contraction can result in significant misalignment and blurring of structures within the thorax and upper abdomen, reducing quantitative accuracy of radiotracer uptake such as SUV and accurate volume definition in PET images.3 Thus, it causes not only the misdiagnosis of lesion location but also errors of quantification.6

To reduce respiration-induced artifacts, 2 techniques have been developed recently in human medicine: respiratory gating and deep-inspiration breath-hold PET/CT.2,7 These techniques can improve accuracy of quantification of both maximum SUV and metabolic volume in lesions located close to the diaphragm and thereby influenced by respiratory motion.2,8 Disadvantages of respiratory gating PET/CT are the need for dedicated hardware and software, the technical effort and costs, a long acquisition time for processing the examination, and high radiation exposure.6,7 In contrast, breath-hold PET/CT technique is easy to implement in clinical practice.6 Before these methods were developed, diagnostic PET/CT scans had been often obtained by using spontaneous ventilation (SV) PET acquisitions and end-expiration, breath-hold CT acquisition, an approach known to minimize, but not eliminate, respiratory misregistration.911 While voluntary breath-hold is not possible in veterinary patients under general anesthesia, positive pressure breath-hold (PPBH) has been widely applied for CT scans to decrease respiratory motion artifacts.12

In 1 study,13 the most common PET/CT artifacts in dogs and cats were related to misregistration from respiratory motion artifacts, which was found in one-third of patients. It has been shown in dogs that the minimum values of diaphragmatic excursion were 2.85 to 2.98 mm during normal breathing, and that median and maximum displacement of the liver in all directions was 4.3 and 23.6 mm, respectively in ventral recumbency.14,15 Although the effects of breathing protocols on motion artifacts have been reported frequently in human PET/CT, there is little information in veterinary medicine.2,3,6,7 The aim of the present study was to investigate the feasibility of PPBH PET/CT in terms of respiration-induced artifact reduction. For this purpose, we compared the quality of PET images, the misalignment of organs on fused PET/CT images, and SUVs of the liver adjacent to the diaphragm between SV and PPBH techniques. We hypothesized that PPBH PET/CT would provide higher image quality and less degree of misalignment than those in SV PET/CT, which would lead to more accurate SUV quantification of the liver near the diaphragm.

Materials and Methods

Animals

The study was approved by and conducted in accordance with the Institutional Animal Care and Use Committee of the University of California-Davis. Five female purpose-bred mixed-breed dogs were enrolled in this experimental study. The median weight of all dogs was 22.7 kg (range, 20 to 24.5 kg), and the median age was 26 months (range, 25 to 27 months). The dogs were considered to be healthy based on physical exam, results of laboratory testing, thoracic and abdominal radiography, and abdominal ultrasound examination. Blood glucose measured before 2-([18F]fluoro)-2-deoxy-D-glucose (18FDG) administration was within the reference range (60 to 111 mg/dL) in all dogs.16 All dogs were fasted for 12 hours before 18FDG administration. A peripheral IV catheter was inserted into the cephalic vein for drug administration.

Dogs were anesthetized using the following protocol. General anesthesia was induced with propofol to effect (4.4 to 7.5 mg/kg, IV) and maintained with isoflurane and oxygen using a cuffed endotracheal tube. Lactated Ringer solution was administered IV at 3 mL/kg/h throughout the anesthetic period. Body temperature was maintained using a warm air circulating blanket. Blood pressure, heart rate, and respiratory rate were monitored throughout the scanning procedure.

Image acquisition

All PET/CT images were acquired using a PET/CT (Siemens Biograph-16; Siemens Medical Solutions USA Inc) with a 16-slice CT subsystem and a PET subsystem with lutetium oxyorthosilicate detectors. All dogs were anesthetized and positioned in sternal recumbency on the PET/CT couch. This position was maintained throughout the PET/CT scans. A low-radiation dose, non-contrast medium–enhanced CT scan was performed for attenuation correction and anatomic localization prior to the PET examination. CT scanning parameters included 50 mAs and 120 kV, with online tube current modulation (CARE Dose4D; Siemens). All PET images were reconstructed using iterative algorithms (the Fourier rebinning order-subset expectation maximization, 2 iterations, 8 subsets, and 4-mm Gaussian filter) with CT-based attenuation correction. The data were reconstructed with a 128 X 128 matrix and 3-mm slice thickness.

A single IV dose of 18FDG at 2.0 to 3.9 mCi (median, 3.5 mCi) was administered to anesthetized dogs. At 1 hour after 18FDG injection, SV PET/CT images were obtained in 8 bed positions (acquisition time, 3 min/bed) from the head to the femur. A PPBH PET/CT scan centered over the diaphragm was performed following the SV PET/CT scan. For the PPBH, manual compression of a reservoir bag was performed to achieve a positive end-inspiration pressure of 10 cm H2O. PPBH CT images were acquired from the thorax to midabdomen. PPBH PET images were obtained in a single bed position (acquisition time, 1.5 minutes) from the caudal thorax to the cranial abdomen, including left ventricle, liver, and gall bladder, and vertebrae (from ninth thoracic vertebra to second lumbar vertebra). The scan duration for each PET/CT protocol and the time interval between the 2 PET scans was recorded.

Image analysis

Image interpretations were performed on a DICOM viewer software (RadiAnt DICOM Viewer version 2020.1.1; Medixant) that can display 3 orthogonal planes (sagittal, dorsal, and transverse planes) for CT, PET, and PET/CT fused images and all evaluations were carried out in an unblinded manner. The subjective PET image quality was evaluated by 2 board-certified veterinary radiologists (ALZ and EMM) and a veterinarian with 6 years of diagnostic imaging experience (SKC) as a consensus. All quantitative evaluations were done by one observer (SKC) to ensure reproducibility and avoid interobserver variability.

For the image quality evaluation, 3 observers assessed SV and PPBH PET images from the caudal thorax to cranial abdomen in the transverse plane using a 5-point scale for each dog. Observers were allowed to manually adjust the intensity window setting so that each organ appeared light to midgray on the gray scale. The image quality was scored in 3 categories: the overall image quality (ranging from 1 [nondiagnostic image quality] to 5 [excellent image quality]), image noise (ranging from 1 [marked image noise] to 5 [no perceivable image noise]), and conspicuity of anatomic structures in the caudal thoracic region including the mediastinum, thoracic wall, and diaphragm (ranging from 1 [poor conspicuity] to 5 [excellent conspicuity]). The score of 3 was given if the image quality is substantially corresponding to the common FDG PET/CT image quality established as a clinical routine in our institution. Each parameter was averaged for the 5 dogs for statistical analysis.

Quantitative evaluations included assessment of the misalignment between PET and CT images and SUVs of liver adjacent to the diaphragm in SV and PPBH PET/CT images. Four anatomic locations were selected to evaluate the degree of misalignment: left ventricle, liver, gall bladder, and vertebrae (from T9 to L2). The misalignment was defined as any perception of the change in organ contour between the PET and CT images on fused PET/CT images. The degree of misalignment was assessed by measuring the largest distance of misalignment perpendicular to the surface of each organ on each reconstructed PET/CT image (transverse, dorsal, and sagittal plane). If a misaligned left ventricle was superimposed on the liver or if 18FDG excretion into the gall bladder was present, these areas were excluded from measurement in the liver and gall bladder. Identification of 18FDG excretion in bile was defined as focally increased radiopharmaceutical activity within the gall bladder on PET images.

SUVs (maximum SUV, mean SUV, and minimum SUV) were measured in the liver adjacent to the diaphragm to evaluate the effect of respiratory motion artifacts on quantification. SUVs were calculated by use of normalization with the injected 18FDG dose and body weight. First, 3 oval and manual trace regions of interest (ROIs) were drawn on the liver on 3 consecutive transverse images where the caudal vena cava completely enters the liver. Locations of the 3 ROIs were adjacent to the left diaphragmatic dome and on the right and left lateral liver border, avoiding any hepatic vessels or lung on transverse SV CT images. Then, the ROIs were copied and pasted on the same anatomic location of the liver in PPBH CT images (Figure 1), and each CT image was fused with the PET image for acquiring SUVs. The width of the oval ROI was < 10 mm, and the length-to-width ratio was > 2 with an area > 150 mm2. A mean value for each ROI was calculated to provide a weighted average of the SUVs.

Figure 1
Figure 1

Transverse spontaneous ventilation (SV; A) and positive-pressure breath-hold (PPBH; B) CT images of a healthy female mixed-breed dog showing 3 liver regions of interest adjacent to the diaphragm. The oval regions of interest were drawn on the liver adjacent to the right lateral border (dotted line), left diaphragmatic dome (dashed line), and left lateral border (solid line) at the level where the caudal vena cava completely enters into the liver (A; arrow).

Citation: American Journal of Veterinary Research 83, 5; 10.2460/ajvr.21.08.0102

Statistical analysis

Data were analyzed with commercially available software (SPSS version 25.0; IBM Corp). Because of the small sample size, the Wilcoxon signed rank test was used to compare 3 image-quality parameters, degree of organ misalignment on fused PET, and SUVs of liver between SV and PPBH PET/CT scans. A value of P < 0.05 was considered statistically significant.

Results

There were no clinical problems associated with anesthesia or PET/CT imaging. The median durations of scanning for SV and PPBH PET/CT were 26.8 minutes (range, 25 to 31 minutes) and 3 minutes (range, 2 to 5.5 minutes), respectively. The median time interval between the SV and PPBH PET scan was 11 minutes (range, 9 to 30 minutes).

With regard to the qualitative assessment of PET images, the scores of overall image quality and conspicuity of anatomic structures were significantly higher in PPBH than those in SV (Table 1; Figure 2). However, there was no significant difference between PPBH and SV in terms of image noise.

Table 1

Median (range) image quality scores* for positron electron tomography (PET) images of 5 healthy female mixed-breed dogs in spontaneous ventilation (SV) and positive-pressure breath-hold (PPBH) when the images were evaluated by consensus between 3 observers.

Image qualitySVPPBHP value
Overall image quality2 (2–3)3 (3–4)0.025
Image noise5 (2–5)3 (3–4)0.102
Conspicuity of anatomic structures3 (2–3)4 (3–5)0.038

*Scores were assigned on a 5-point scale (1 = poor and 5 = excellent).

Figure 2
Figure 2

SV (A and C) and PPBH (B and D) transverse positron emission tomography (PET) images at the level of the left ventricle (A and B) and liver (C and D) in 5 healthy female mixed-breed dogs. SV PET images were acquired at 3 min/bed position; PPBH PET images at 1.5 min/bed position. Overall image quality and conspicuity of anatomic organs were superior in PPBH than in SV PET images without a difference in image noise. Superimposition of the liver (star) on the left ventricle was shown as the result of motion artifacts from SV (A). The thoracic wall, descending aorta (A, B, and D; black arrow), caudal vena cava (B; white arrow), and diaphragm (C and D; white arrowheads) were more clearly identifiable in PPBH PET images. L = Liver. V = Left ventricle. W = Thoracic wall.

Citation: American Journal of Veterinary Research 83, 5; 10.2460/ajvr.21.08.0102

The degree of misalignment for each organ in fused PET/CT images was summarized (Table 2). PPBH induced significantly less misalignment of the left ventricle and liver in all directions compared to SV (Figure 3). While the left ventricle was superimposed on the liver in 4 of 5 dogs during SV PET/CT, it was not observed in any of the dogs during PPBH PET/CT. For the gall bladder, PPBH showed significantly less misalignment than SV in the transverse plane, but not in the dorsal and sagittal planes. Among the 5 dogs, 18FDG excretion in bile was identified in 3 and 4 dogs during SV and PPBH PET/CT, respectively. There was no significant difference in misalignment between SV and PPBH PET/CT in the vertebrae.

Table 2

Median (range) distance (mm) of misalignment for each organ of 5 healthy female mixed-breed dogs on the 3 planes of fused PET/CT images in SV and PPBH.

OrganDistance of misalignment (mm)P value
TransverseDorsalSagittalTransverseDorsalSagittal
Left ventricleSV23 (18.8–28.4)15.2 (11.3–24.5)15.3 (8.2–26.1)0.040.040.04
PPBH13 (10.4–14.4)9.2 (1–11.2)7.9 (7.5–11.8)
LiverSV11.2 (8.8–21)11.5 (7–13.5)10.6 (7.4–15.4)0.040.040.04
PPBH7.4 (1.3–9.4)5.6 (3.4–6.3)3.5 (2.2–4.9)
Gall bladderSV9.5 (7.8–11.5)9.4 (8.4–18.3)9 (8.3–12.8)0.040.140.08
PPBH6.9 (6.4–9.5)9.6 (5.4–11.3)6.5 (5.0–9.3)
VertebraeSV3.2 (2.9–4.5)3.7 (0–6.8)3.3 (0–4.0)0.890.460.27
PPBH3.6 (0–4.4)2.6 (0–3.5)2.2 (0–3.2)
Figure 3
Figure 3

Transverse (A and B), dorsal (C and D), and sagittal (E and F) PET/CT images of the caudal thoracic region in SV (A, C, and E) and PPBH (B, D, and F) procedures in a healthy female mixed-breed dog. Compared with PPBH PET/CT images, SV PET/CT images showed a greater degree of misalignment of the left ventricle (white arrows) and liver (white arrowheads) in all planes and increased misalignment of gall bladder (white-outlined arrowhead) on the transverse plane. Superimposition of the left ventricle (star) on the liver was due to motion artifacts in SV PET.

Citation: American Journal of Veterinary Research 83, 5; 10.2460/ajvr.21.08.0102

Maximum SUV, mean SUV, and minimum SUV were measured for each liver ROI adjacent to the diaphragm (Table 3). The maximum SUV in all liver ROIs was significantly higher in PPBH compared to SV. In addition, PPBH showed significantly higher mean SUV in liver ROIs adjacent to the left lateral border and the left diaphragmatic dome and higher minimum SUV in liver ROI adjacent to the left diaphragmatic dome.

Table 3

Median (range) standardized uptake values (SUVs) of the 3 liver regions of interest adjacent to the diaphragm in SV and PPBH PET/CT images for 5 healthy female mixed-breed dogs.

LocationStatisticSVPPBHP value
Right lateral borderMean SUV0.99 (0.79–1.7)1.41 (0.75–1.8)0.08
Maximum SUV1.04 (0.88–1.81)1.49 (1–2.03)0.04
Minimum SUV0.92 (0.73–1.55)1.03 (0.64–1.44)0.34
Left diaphragmatic domeMean SUV0.96 (0.73–1.43)1.36 (0.88–1.9)0.04
Maximum SUV1.01 (0.78–1.58)1.46 (1–2.03)0.04
Minimum SUV0.93 (0.66–1.33)1.16 (0.74–1.65)0.04
Left lateral borderMean SUV0.9 (0.62–1.68)1.14 (0.79–1.77)0.04
Maximum SUV1.05 (0.68–1.74)1.24 (0.94–1.92)0.04
Minimum SUV0.83 (0.54–1.62)1.03 (0.61–1.51)0.14

Discussion

Inspiratory breath-hold PET/CT is widely used for the identification of thoracic and abdominal lesions in human medicine. This technique reduces motion artifacts on PET/CT images, which include PET/CT misalignment and lesion blurring and, consequently, can improve the accuracy of SUV quantification.17,18 Similarly, the results of the present study demonstrated that PPBH PET/CT showed higher PET image quality, less misalignment of organs on fused PET/CT image, and increased SUV of liver border areas adjacent to the diaphragm versus SV PET/CT.

In this study, the single bed acquisition time was 3 minutes for SV PET scan and 1.5 minutes for PPBH PET scan. The PPBH PET scan was shortened to 1.5 minutes to reduce the chance of resumption of SV despite adequate oxygenation. However, shortened acquisition time could increase the noise of obtained images.19 Although there was a trend toward decreased quality scores in terms of image noise in PPBH, there was no statistically significant difference between PPBH and SV in the present study, and the decreased scan time was deemed acceptable for image noise.

The PPBH resulted in higher scores of overall image quality and conspicuity of anatomic structures than SV. While shorter scan times in PPBH PET scans could have reduced the radioactive signal registered, leading to increased image blurring,20 respiratory motion artifacts in SV PET scans made the margin of anatomic structures even more indistinct. In humans, the acquisition time could be reduced to 60 seconds without decreasing lesion detection rate and changing the maximum SUV of tumors.19 Furthermore, 1 study21 found that optimum emission time > 1.5 minutes of acquisition is preferable for clinical use of inspiratory breath-hold PET/CT. The 1.5-minute acquisition time in the present study was adequate for image signal-to-noise ratio while improving quality by reducing motion artifacts.

In the present study, the misalignment was measured as the greatest distance of misalignment perpendicular to the surface of each organ on fused PET/CT images to reflect the oblique movement of the organs in three planes.22 Our results showed that PPBH technique led to significantly less misalignment of anatomic structures that are located close to the diaphragm, particularly, in the left ventricle and the liver. The fixed respiratory position during PPBH PET/CT scanning resulted in lesser degrees of misalignment in these organs.

Improved alignment of PET and CT images can provide higher diagnostic accuracy of PET/CT for tumor detection.18 One study reported that breath-hold PET/CT corrected the erroneous location of tumor from incorrect to correct organ by 39.3% and from incorrect to correct region within the liver by 60.7%.6 The distance of misalignment > 10 mm is considered to cause ambiguity in discrimination of 2 adjacent small lesions.23 During PPBH, all distances of hepatic misalignment were < 10 mm in all direction, which could make it possible to discriminate between small lesions in the liver.

18FDG excretion in bile was identified and increased in most dogs. This physiological phenomenon needs to be considered for clinical PET study to avoid misinterpretation. PPBH showed significantly less misalignment of gall bladder than SV in the transverse plane only. The increase of 18FDG accumulation in the gall bladder over time could have hindered the accurate measurement of misalignment in the other planes and was therefore excluded.

Accurate quantification of SUV is needed for diagnosis and staging of malignant lesions and assessing the therapeutic response. In all liver ROIs of the present study, the maximum SUV was significantly higher in PPBH compared to SV. Because tracer activity within a liver border area was dispersed with respiratory motion and volume averaging with lung in the SV PET scan, the true concentration of tracer activity was underestimated in this area.6,18 One human study6 found that maximum SUV had increased as much as 50% on average in hepatic lesions on breath-hold PET images compared to SV PET images. Meanwhile, mean SUV and minimum SUV did not show significant differences in some liver ROIs. Given the recent report22 demonstrating asymmetric excursion of diaphragmatic crura, with the right crus showing less excursion than the left crus during SV, asymmetric movements of the diaphragm could have contributed to the higher variability in SUVs on the right lateral border in the present study. In addition, short acquisition time on PPBH PET scanning could be associated with the greater SD of SUV in the liver, which could have caused a decrease in minimum SUV in this study. Reduced 18FDG uptake within the hepatic parenchyma over time after tracer injection could be another contributing factor as PPBH scans were performed after SV scans.24

During breath-hold PET/CT scanning in humans, awake patients are asked to perform breath-holds. The feasibility of breath-hold PET/CT largely depends on a patient’s compliance with breath-hold instructions and general health status.7 On the contrary, in veterinary patients PET/CT scanning is usually performed under general anesthesia, which allows intrathoracic pressure to be maintained in a more constant and reproducible manner during PPBH.

Successful PPBH requires an optimal balance of oxygen and carbon dioxide. There is sufficient oxygenation delivered by anesthetic gas mixtures including high partial pressures oxygen to prevent hypoxemia; however, accumulation of carbon dioxide may trigger SV after 2 to 3 minutes of apnea. Performing hyperventilation prior to the breath hold can decrease the alveolar concentration of carbon dioxide so that the increase occurring during apnea does not reach the threshold to stimulate breathing.

Although no apparent complications related to PPBH were observed in the present study, prolonged apnea during breath-hold could induce hyperinflation and negative cardiovascular effects.25 Positive airway pressure causes an increase in thoracic pressure, resulting in a decrease in venous return in the thoracic cavity, and subsequent decreased stroke volume, cardiac output, and consequently arterial blood pressure.25,26 Therefore, the PPBH PET/CT technique may be contraindicated in dogs affected with hypovolemia or cardiovascular disease.

In the present study, the PPBH PET/CT technique was easy to perform in anesthetized dogs and required only a minimal increase in the examination time. The scanning area was limited to a single bed position and thereby cannot include the entire area of the lungs and potentially enlarged liver.6,17 Moreover, an increase in image noise was shown at the cranial and caudal edges of the scan area.7 Despite the limited field of view, the overall image quality was improved and PPBH could be a complementary option for a whole-body SV scan and may improve lesion detectability and diagnostic accuracy in the diaphragmatic region.6,7,18

The present study had several limitations. The order of the scans was not randomized but instead was performed in the same order for each dog. PPBH was achieved manually by compression of a reservoir bag, which could cause a slight difference in intrathoracic airway pressure between PET and CT scans. The effect of PPBH on the cardiovascular system was evaluated in a limited way. However, additional monitoring including hemoglobin oxygen saturation, cardiac output, and blood gas analysis would be insufficient to detect the degree of change expected in the time frame of the breath-hold. To identify possible cardiovascular impacts in further studies, particularly in critically ill patients, direct arterial pressure could help to detect a drop in blood pressure during PPBH and indicate a need to resume ventilation. Finally, the number of animals used was small and the demographics were limited only to female dogs of similar age and size in this study. Further studies are needed with a large number and a variety of breeds prior to clinical application of the PPBH PET/CT.

In conclusion, the present study compared image quality, degree of misalignment, and SUVs of liver between PPBH and SV PET/CT. PPBH technique demonstrated higher PET image quality, less misalignment of organs on fused PET/CT images, and higher SUV of liver border areas when compared with SV PET/CT scans. These results indicated that PPBH PET/CT was a feasible technique for reducing respiratory motion artifacts and increasing image quality in healthy dogs and has the potential to be useful in clinical veterinary patients with pulmonary and hepatic tumors.

Acknowledgments

No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.

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Contributor Notes

Corresponding author: Dr. Zwingenberger (azwingen@ucdavis.edu)