Targeting Lesion Localization: A New Era
Nuclear medicine techniques have transformed vigorously in the past decade or so, particularly with improving lesion localization in oncology imaging. While conventional planar imaging may still be considered the top choice, SPECT/CT, time-of-flight (TOF) PET/CT and PET/MR, have shown better detection of cancerous lesions. While none of these strategies have been quick to replace gold-standard, conventional screening, their filtration into the market and their capability to perform whole-body scanning with reduced image noise have clinicians evaluating which modality is best for which anatomy.
For example, Kadrmas et al performed a phantom study using an anthropomorphic lesion detection phantom that was scanned 12 times over three days on a TOF PET/CT scanner (Biograph, Siemens Healthcare). Lesions (6 mm to 16 mm in diameters) were placed throughout the phantom and data were reconstructed. Researchers found “significant improvement” with TOF data compared with non-TOF data, concluding that the addition of point spread function modeling to TOF imaging may further improved lesion detection (J Nucl Med 2009;50[8]1315-1323).
Suleman Surti, PhD, research associate of physics and instrumentation in the radiology department at the University of Pennsylvania School of Medicine in Philadelphia, aimed to assess the benefit of using 3D TOF PET scanner (Gemini TF PET/CT, Philips Healthcare) during whole-body oncology scans using human observers to detect lesions in realistic patient anatomic backgrounds.
Surti et al assessed the impact of TOF FDG-PET imaging for lung and liver lesion detection when compared with non-TOF PET/CT. “In some cases with PET, you may garner noisy images,” he says. “During non-TOF data reconstruction, patients may not have a lesion, yet the clinical observer may see a clump in the imaging exam that [could appear to be a lesion, but in fact] may just be noise. With time-of-flight, you may be able to reduce these instances of incorrect lesion localization.”
The researchers included 100 patients with normal F-18 FDG uptake and imaged spheres (1 cm in diameter) in the PET scanner independent of the patient (J Nucl Med 2011;52[5]:712-719). They mulched data from the lesions into real patient data that accounted for the physical effects of attenuation in the scanner.
The researchers reconstructed three image types: no lesions, a lesion placed in the lung and a lesion placed in the liver. Scan times (one minute vs. three minutes), body mass index (BMI) (<26 kg/m2 vs. ?26 kg/m2) and type of imaging (TOF vs. non-TOF) were assessed. Six readers interpreted an average of 720 images.
“In the liver region, we found a statistically significant improvement in the area under the AROC curve for very heavy patients at both one minute and three minutes for time of flight,” Surti says. However, patients with lower BMIs who underwent TOF scanning only saw an improvement with one-minute scans.
“Time-of-flight imaging was always better than non time of flight, whether it was in lighter or heavier patients, or with one- minute or three-minute scans,” says Surti. For lung lesions, which are some of the most challenging to interpret, one-minute scans were of poor quality no matter whether they was performed with TOF or non-TOF imaging, he says.
“The difference between the ALORC values between the two BMI levels is less with the longer scans [three minutes] and was further reduced with the addition of TOF,” Surti notes. TOF imaging added value, no matter the patient’s size or lesion location in the organ. “Without time of flight, you have good performance for lighter patients and poor performance for heavier patients.”
“It will be important for clinicians to note that you cannot just minimize the scan time from three minutes to one minute when using time of flight,” Surti offers. There are still some scenarios, such as lung imaging and imaging heavier patients, where the three-minute scan will be necessary.
“[TOF] improves the diagnosis for challenging situations where you would otherwise miss lesions,” he adds. While this may not be largely important with metastasis, due to the soft lesions, with borderline lesion detection time of flight provides more clinical confidence. “The error bar is narrowed with time of flight.”
PET/CT has limitations in certain clinical situations, such as central nervous system disorders or during metastatic disease follow up, says Zaidi. In 2010, Boss et al tested the practicability of using PET/MR to image malignant head and neck tumors (Eur Radiology 2011;21:1439-1446). PET/MR had better image resolution and image contrast compared with PET/CT in the eight patients enrolled, the researchers found.
In their own phantom study, Zaidi and colleagues compared the results of a hybrid TOF PET/MR system (Ingenuity, Philips) with the TOF PET/CT scanner (Gemini TF) (Phys Med Biol 2011;56[10]:3091-3096). “The performance of the PET subsystem was comparable with the TOF PET/CT system using phantom and patient studies,” Zaidi says.
He and colleagues reported that the timing of the PET/MR measured 525 picoseconds (ps), which is comparable to the 500 ps to 600 ps of PET/CT scanners, according to Surti. In addition, energy resolution of the PET/MR system was tracked at 12 percent. But in terms of workflow, PET/MR acquisitions may take longer compared with PET/CT, Zaidi adds.
While study results were promising, Zaidi says the use of PET/MR in clinical practice is still in the “embryonic stage,” and remains controversial. Many larger clinical trials are needed to assess the strengths of PET/CT vs. PET/MR, he notes.
While the technology may be helpful, Zaidi says several technical challenges exist including interference between the PET and MRI modalities. “MRI-guided attenuation correction remains a challenging issue that needs to be addressed since it generates visible artifacts and in some cases, introduces significant bias [particularly in bone lesions] where tracer uptake is sometimes underestimated,” he adds.
Despite these challenges, Zaidi says, the “recent introduction of PET/MR technology is considered by many experts as a major breakthrough that will potentially lead to a revolutionary paradigm shift in healthcare and revolutionize clinical practice.”
While most nuclear imaging centers still use 2D planar imaging techniques, some are opting for quicker whole-body scans using 3D SPECT/CT imaging protocols.
“Whole-body scans are used for discovering metastasis in the bones that stem from tumors,” says Anna Cellar, PhD, head of the Medical Imaging Research Group in Vancouver, British Columbia, and professor in the department of radiology at the University of British Columbia. However, the 2D planar mode just doesn’t cut it. Thus, Cellar and her colleagues evaluated whether a protocol using Tc-99m whole-body SPECT bone scanning could be performed at faster speeds with lower doses of radioisotopes in a Phase II study.
“Normally, SPECT [exams] take more time,” Cellar says. “But, if you perform resolution recovery during SPECT scans, you can do the same injections in the same time and get a much better image.”
With planar imaging, the camera is stopped at different anatomical positions for 20 seconds; however, today’s cameras allow data to be collected at various time frames and anatomical positions (for example, 10 to 20 frames per second).
During the open Phase II study (for which data are not yet published), Cellar and colleagues compared malignant lesions with whole-body F-18 PET and Tc-99m SPECT in patients with metastatic skeletal bone lesions. The researchers also compared SPECT scans with standard planar scans. Twenty-five subjects were expected to be enrolled to undergo planar bone scintigraphy, bone SPECT and F-18 whole-body PET scans.
Patients were analyzed by three independent nuclear medicine readers and lesions were detected with planar scans then compared with lesions on non-Astonish [Philips] SPECT bone scans and Astonish SPECT bone scans. PET/CT bone scans were used as the gold-standard.
“We found that we can acquire the data almost as fast as the planar mode and acquire 3D information,” Cellar says. The whole-body SPECT/CT bone scans with de-blurring protocol took an estimated 20 minutes and resulted in both better attenuation and resolution recovery.
“We can do these scans very rapidly now,” says Philip F. Cohen, MD, division head of nuclear medicine at the Lions Gate Hospital in Vancouver. “Once clinicians start doing SPECT/CT, they will find that they are getting PET-like images at comparable scan speeds.
“We think this will be the most sensitive way of performing bone lesion imaging tests [with full-body SPECT/CT],” Cohen says. “We replace the standard nuclear technique with a more advanced technique taking the same amount of time, but collecting much more information.”
While the study set out to compare the gold-standard of F-18 PET bone scans with whole-body Tc-99m SPECT, Cohen says PET cameras are hard to come by in Canada and the researchers have not yet been able to conduct the next arm of the trial. Therefore, the study has been halted. “There are two PET scanners in British Columbia, but they are not yet developed to perform these types of bone scans,” Cohen adds.
While some may be hesitant to believe that PET and SPECT/CT have comparable image sensitivity; Cohen says, so far, obtained images have been “very, very comparable.”
Globally, nuclear medicine researchers question which modality can produce high-quality images at a lower price tag? PET scanners are costly and could rack up a bill of nearly $2 million compared with $500,000 for a SPECT/CT scanner, says Cohen.
In addition, SPECT/CT may win out in terms of feasibility due to the fact that the Tc-99m radiotracer is more widely available when compared with F-18, which must be housed in a cyclotron. While SPECT/CT may be cheaper, more readily available and comparable to PET, Cohen says it may never top the image resolutions obtained with PET modalities.
“As everyone moves to doing whole-body SPECT or whole-body SPECT/CT, images will come close to what you can achieve with F-18, which is the gold standard in nuclear medicine and probably be as good as MRI,” Cohen sums.
Greater attenuation, faster scan speeds and improved lesion detection are just some of the benefits of hybrid and combined nuclear imaging modalities in terms of the better detection of lesion localization.
“The clinical role of multi-modality imaging encompasses a wide variety of applications and now is performed routinely with commercially available radiopharmaceuticals to answer important clinical questions including those in oncology, cardiology and neurology,” Zaidi sums.
While the capabilities of SPECT/CT, PET/MR and PET/CT whole-body imaging advances are still emerging in the field of oncology, it remains to be seen which modalities will be best for which types of lesions and patients in terms of cost, attenuation, resolution and scan speed.
Time to fly
Previous phantom studies have shown improved lesion detection with TOF PET/CT scanners. However, results of these phantom studies may mask how key findings will fare in a real-world cohort.For example, Kadrmas et al performed a phantom study using an anthropomorphic lesion detection phantom that was scanned 12 times over three days on a TOF PET/CT scanner (Biograph, Siemens Healthcare). Lesions (6 mm to 16 mm in diameters) were placed throughout the phantom and data were reconstructed. Researchers found “significant improvement” with TOF data compared with non-TOF data, concluding that the addition of point spread function modeling to TOF imaging may further improved lesion detection (J Nucl Med 2009;50[8]1315-1323).
Suleman Surti, PhD, research associate of physics and instrumentation in the radiology department at the University of Pennsylvania School of Medicine in Philadelphia, aimed to assess the benefit of using 3D TOF PET scanner (Gemini TF PET/CT, Philips Healthcare) during whole-body oncology scans using human observers to detect lesions in realistic patient anatomic backgrounds.
Surti et al assessed the impact of TOF FDG-PET imaging for lung and liver lesion detection when compared with non-TOF PET/CT. “In some cases with PET, you may garner noisy images,” he says. “During non-TOF data reconstruction, patients may not have a lesion, yet the clinical observer may see a clump in the imaging exam that [could appear to be a lesion, but in fact] may just be noise. With time-of-flight, you may be able to reduce these instances of incorrect lesion localization.”
The researchers included 100 patients with normal F-18 FDG uptake and imaged spheres (1 cm in diameter) in the PET scanner independent of the patient (J Nucl Med 2011;52[5]:712-719). They mulched data from the lesions into real patient data that accounted for the physical effects of attenuation in the scanner.
The researchers reconstructed three image types: no lesions, a lesion placed in the lung and a lesion placed in the liver. Scan times (one minute vs. three minutes), body mass index (BMI) (<26 kg/m2 vs. ?26 kg/m2) and type of imaging (TOF vs. non-TOF) were assessed. Six readers interpreted an average of 720 images.
“In the liver region, we found a statistically significant improvement in the area under the AROC curve for very heavy patients at both one minute and three minutes for time of flight,” Surti says. However, patients with lower BMIs who underwent TOF scanning only saw an improvement with one-minute scans.
“Time-of-flight imaging was always better than non time of flight, whether it was in lighter or heavier patients, or with one- minute or three-minute scans,” says Surti. For lung lesions, which are some of the most challenging to interpret, one-minute scans were of poor quality no matter whether they was performed with TOF or non-TOF imaging, he says.
“The difference between the ALORC values between the two BMI levels is less with the longer scans [three minutes] and was further reduced with the addition of TOF,” Surti notes. TOF imaging added value, no matter the patient’s size or lesion location in the organ. “Without time of flight, you have good performance for lighter patients and poor performance for heavier patients.”
“It will be important for clinicians to note that you cannot just minimize the scan time from three minutes to one minute when using time of flight,” Surti offers. There are still some scenarios, such as lung imaging and imaging heavier patients, where the three-minute scan will be necessary.
“[TOF] improves the diagnosis for challenging situations where you would otherwise miss lesions,” he adds. While this may not be largely important with metastasis, due to the soft lesions, with borderline lesion detection time of flight provides more clinical confidence. “The error bar is narrowed with time of flight.”
Will PET/MR be better?
PET/CT has advanced as the whole-body scanning modality of choice for tumor assessment; however, PET/CT may be limited in some clinical scenarios, especially in its ability to detect soft-tissue, says Habib Zaidi, PhD, head of PET instrumentation and neuroimaging laboratory at Geneva University Hospital in Geneva, Switzerland. But, what PET/CT lacks, MRI may make up for with added sensitivity and function. “The combination of PET and MRI bridges the gap between molecular and systems diagnosis,” notes Zaidi.PET/CT has limitations in certain clinical situations, such as central nervous system disorders or during metastatic disease follow up, says Zaidi. In 2010, Boss et al tested the practicability of using PET/MR to image malignant head and neck tumors (Eur Radiology 2011;21:1439-1446). PET/MR had better image resolution and image contrast compared with PET/CT in the eight patients enrolled, the researchers found.
In their own phantom study, Zaidi and colleagues compared the results of a hybrid TOF PET/MR system (Ingenuity, Philips) with the TOF PET/CT scanner (Gemini TF) (Phys Med Biol 2011;56[10]:3091-3096). “The performance of the PET subsystem was comparable with the TOF PET/CT system using phantom and patient studies,” Zaidi says.
He and colleagues reported that the timing of the PET/MR measured 525 picoseconds (ps), which is comparable to the 500 ps to 600 ps of PET/CT scanners, according to Surti. In addition, energy resolution of the PET/MR system was tracked at 12 percent. But in terms of workflow, PET/MR acquisitions may take longer compared with PET/CT, Zaidi adds.
While study results were promising, Zaidi says the use of PET/MR in clinical practice is still in the “embryonic stage,” and remains controversial. Many larger clinical trials are needed to assess the strengths of PET/CT vs. PET/MR, he notes.
While the technology may be helpful, Zaidi says several technical challenges exist including interference between the PET and MRI modalities. “MRI-guided attenuation correction remains a challenging issue that needs to be addressed since it generates visible artifacts and in some cases, introduces significant bias [particularly in bone lesions] where tracer uptake is sometimes underestimated,” he adds.
Despite these challenges, Zaidi says, the “recent introduction of PET/MR technology is considered by many experts as a major breakthrough that will potentially lead to a revolutionary paradigm shift in healthcare and revolutionize clinical practice.”
SPECT/CT: No bones about it
Bone scanning with Tc-99m diphosphonates is commonly used in the survey of metastatic cancers, and other scenarios; however, the technology has not undergone significant updates since the 1970s. Despite the added sensitivity with SPECT when compared with standard planar bone studies, the use of the modality is often limited due to lengthy scan times.While most nuclear imaging centers still use 2D planar imaging techniques, some are opting for quicker whole-body scans using 3D SPECT/CT imaging protocols.
“Whole-body scans are used for discovering metastasis in the bones that stem from tumors,” says Anna Cellar, PhD, head of the Medical Imaging Research Group in Vancouver, British Columbia, and professor in the department of radiology at the University of British Columbia. However, the 2D planar mode just doesn’t cut it. Thus, Cellar and her colleagues evaluated whether a protocol using Tc-99m whole-body SPECT bone scanning could be performed at faster speeds with lower doses of radioisotopes in a Phase II study.
“Normally, SPECT [exams] take more time,” Cellar says. “But, if you perform resolution recovery during SPECT scans, you can do the same injections in the same time and get a much better image.”
With planar imaging, the camera is stopped at different anatomical positions for 20 seconds; however, today’s cameras allow data to be collected at various time frames and anatomical positions (for example, 10 to 20 frames per second).
During the open Phase II study (for which data are not yet published), Cellar and colleagues compared malignant lesions with whole-body F-18 PET and Tc-99m SPECT in patients with metastatic skeletal bone lesions. The researchers also compared SPECT scans with standard planar scans. Twenty-five subjects were expected to be enrolled to undergo planar bone scintigraphy, bone SPECT and F-18 whole-body PET scans.
Patients were analyzed by three independent nuclear medicine readers and lesions were detected with planar scans then compared with lesions on non-Astonish [Philips] SPECT bone scans and Astonish SPECT bone scans. PET/CT bone scans were used as the gold-standard.
“We found that we can acquire the data almost as fast as the planar mode and acquire 3D information,” Cellar says. The whole-body SPECT/CT bone scans with de-blurring protocol took an estimated 20 minutes and resulted in both better attenuation and resolution recovery.
“We can do these scans very rapidly now,” says Philip F. Cohen, MD, division head of nuclear medicine at the Lions Gate Hospital in Vancouver. “Once clinicians start doing SPECT/CT, they will find that they are getting PET-like images at comparable scan speeds.
“We think this will be the most sensitive way of performing bone lesion imaging tests [with full-body SPECT/CT],” Cohen says. “We replace the standard nuclear technique with a more advanced technique taking the same amount of time, but collecting much more information.”
While the study set out to compare the gold-standard of F-18 PET bone scans with whole-body Tc-99m SPECT, Cohen says PET cameras are hard to come by in Canada and the researchers have not yet been able to conduct the next arm of the trial. Therefore, the study has been halted. “There are two PET scanners in British Columbia, but they are not yet developed to perform these types of bone scans,” Cohen adds.
While some may be hesitant to believe that PET and SPECT/CT have comparable image sensitivity; Cohen says, so far, obtained images have been “very, very comparable.”
Globally, nuclear medicine researchers question which modality can produce high-quality images at a lower price tag? PET scanners are costly and could rack up a bill of nearly $2 million compared with $500,000 for a SPECT/CT scanner, says Cohen.
In addition, SPECT/CT may win out in terms of feasibility due to the fact that the Tc-99m radiotracer is more widely available when compared with F-18, which must be housed in a cyclotron. While SPECT/CT may be cheaper, more readily available and comparable to PET, Cohen says it may never top the image resolutions obtained with PET modalities.
“As everyone moves to doing whole-body SPECT or whole-body SPECT/CT, images will come close to what you can achieve with F-18, which is the gold standard in nuclear medicine and probably be as good as MRI,” Cohen sums.
Greater attenuation, faster scan speeds and improved lesion detection are just some of the benefits of hybrid and combined nuclear imaging modalities in terms of the better detection of lesion localization.
“The clinical role of multi-modality imaging encompasses a wide variety of applications and now is performed routinely with commercially available radiopharmaceuticals to answer important clinical questions including those in oncology, cardiology and neurology,” Zaidi sums.
While the capabilities of SPECT/CT, PET/MR and PET/CT whole-body imaging advances are still emerging in the field of oncology, it remains to be seen which modalities will be best for which types of lesions and patients in terms of cost, attenuation, resolution and scan speed.