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- Computed Tomography | Image Wisely
- Single Photon Emission Computed Tomography (SPECT)
Ventilation studies are in general performed after inhalation of Kr-labelled or technetium-labelled aerosol of diethylene triamine pentaacetic acid DTPA or Technegas. Perfusion studies are performed after intravenous injection of macro-aggregated human albumin. Radiation exposure using documented isotope doses is 1. The EANM's practice guidelines on VP scintigraphy also noted that to reduce the costs, the risks associated with false-negative and false-positive diagnoses, and unnecessary radiation exposure, pre-imaging assessment of clinical probability is recommended.
It is particularly favored in young patients, especially females, during pregnancy, and for follow-up and research Bajc et al, b. Single photon emission computed tomography has proven useful in distinguishing lymphoma from necrosis in the chest and abdomen. It is also useful in localizing abscesses, and distinguishing abscess from other infectious or inflammatory processes. Single photon emission computed tomography is also useful in osteomyelitis in distinguishing inflammation of soft tissue from bone.
Guidelines on parathyroid scintigraphy from the Society of Nuclear Medicine Greenspan et al, state that there is a developing consensus that SPECT imaging is useful, because, when used in conjunction with planar imaging, SPECT provides increased sensitivity and more precise anatomic localization. They note that this is particularly true in detecting both primary and recurrent hyperparathyroidism resulting from ectopic adenomas. In the mediastinum, accurate localization may assist in directing the surgical approach, such as median sternotomy versus left or right thoracotomy.
However, its use as a routine procedure before target surgery is still investigational. In a review on neuroimaging in psychopathy including anti-social personality disorder and violent behavior , Pridmore et al noted that functional neuroimaging strongly suggests dysfunction of particular frontal and temporal lobe structures in subjects with psychopathy. However, there are difficulties in selecting homogeneous index cases and appropriate control groups.
These investigators stated that further studies are needed. Single photon emission computed tomography has also been able to identify decreases in frontal cortex uptake that are associated with negative symptoms of schizophrenia. The investigators, however, were unable to find substantial evidence for the role of SPECT scans in therapeutic decision-making in schizophrenia.
In a meta-analysis of the literature on diagnostic accuracy of SPECT in parkinsonian syndromes, Vlaar and colleagues concluded that SPECT with pre-synaptic radiotracers is relatively accurate to differentiate patients with PD in an early phase from normalcy, patients with PD from those with essential tremor, and PD from vascular parkinsonism. The accuracy of SPECT with both pre-synaptic and post-synaptic tracers to differentiate between PD and atypical parkinsonian syndrome is relatively low.
This diminished width probably reflects selective neuronal loss of the pars compacta. Other authors have found a normal appearance of the substantia nigra on T2-weighted images in a majority of PD patients. More recently, PET and SPECT tracer studies exploring the presynaptic nigrostriatal terminal function and the postsynaptic dopamine receptors have attempted to classify the various Parkinson syndromes although much of this work remains investigational".
These researchers noted that PET and SPECT may be used to assess plaque vulnerability, biology of aneurysm progression, prosthetic graft infection, and vasculitis. Moreover, the authors stated that considerable further information will be needed to define whether and where PET or SPECT will fit in a clinical strategy. The necessary validation studies represent an exciting challenge for the future but also may require the development of inter-disciplinary imaging groups to integrate expertise and optimize nuclear diagnostic potential.
The report stated that SPECT-CT imaging is being explored in a wide range of cancers for a variety of purposes, and , that there is some evidence of an evolving role in specific areas such as lymph node assessment and mapping and the identification of bone metastases. In particular there is a need to compare the clinical utility of hybrid scanners using low performance X-ray scanners with the newer multislice machines to assess the additional benefits of the new generation scanners in clinical practice.
Technical quality and the severity and extent of radiotracer defects in the upper and lower halves of the lungs were scored from visual inspection of planar scans and SPET data separately. An emphysema index EI extent x severity for the upper and lower halves of the lung, and an EI ratio for upper to lower lung were calculated for both planar and SPET scans. The ratios were compared with post-LVRS outcomes, 3, 6 and 12 months after surgery. All perfusion and SPET images were technically adequate.
Forty-six percent of ventilation scans were not technically adequate due to central airway tracer deposition. Aerosol DTPA ventilation scans are not consistently useful. Perfusion lung scanning may be useful in selecting patients with successful outcomes after LVRS. Nakai et al reported the case of an year old woman who presented with persistent type II endoleak with sac expansion from 57 mm to 75 mm during 4-year follow-up after endovascular abdominal aortic aneurysm repair.
Because of the anticipated embolization artifacts on follow-up computed tomography CT , technetiumm-labeled human serum albumin diethylenetriamine pentaacetic acid single-photon emission computed tomography 99m Tc-HSAD SPECT was performed before and after the intervention. The authors noted that CT scan performed 12 months after embolization showed no signs of sac expansion; and they stated that 99m Tc-HSAD SPECT may be useful for evaluating therapeutic effect after embolization for endoleak.
Local ethics committee approval was obtained, and 34 patients were examined after giving written informed consent. Data were reconstructed and transferred to a US system. The combination of 2 independent positioning systems enabled real-time fusion of metabolic and morphologic information during US examination.
Quality of automatic co-registration was evaluated visually, and deviation was determined by measuring the distance between the center of tracer distribution and the center of the US correlate. All examinations were technically successful. For 18 of 34 examinations, the automatic co-registration and image fusion exhibited very good agreement, with no deviation.
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SPECT artifacts occurred even in situations of clear thyroid findings e. Ryken et al determined which imaging techniques most accurately differentiate true tumor progression from pseudo-progression or treatment-related changes in patients with previously diagnosed glioblastoma. The authors stated that the following recommendations apply to adults with previously diagnosed glioblastoma who are suspected of experiencing progression of the neoplastic process:.
A total of 11 studies 1, participants met inclusion criteria. These consisted of 6 case-control studies, 2 retrospective cohort studies and 3 prospective cohort studies; 3 studies used single-headed camera SPECT while the remaining 8 used multiple-headed camera SPECT. Study design and methods varied widely. Overall, participant selection was not well-described and the studies were judged as having either high or unclear risk of bias.
Often the threshold used to define a positive SPECT result was not pre-defined and the results were reported with knowledge of the reference standard. Concerns regarding applicability of the studies to the review question were generally low across all 3 domains participant selection, index test and reference standard. Sensitivities were lower for the 2 single-headed camera studies; 1 reported a sensitivity and specificity of 0.
Of these studies, 5 used a case-control design and reported sensitivities of between 0. The remaining 3 studies used a cohort design and reported sensitivities of between 0. The authors concluded that they would not recommend the routine use of rCBF SPECT in clinical practice because there is insufficient evidence from the available literature to support this. The authors stated that more prospective cohort studies that verify the presence or absence of FTD during a period of follow-up should be undertaken.
Thoracoscopic abrasion of the parietal pleura was performed, but an important air leak persisted. Presumed to originate from a bulla in the right upper lobe, bullectomy and pleural decortication were performed, but leakage remained. The air leak resolved after conservative treatment. The PubMed and Embase databases were comprehensively searched for relevant articles that evaluated lung lesions suspicious for malignancy.
Two reviewers independently extracted the data on study characteristics and examination results, and assessed the quality of each selected study. The data extracted from the eligible studies were assessed by heterogeneity and threshold effect tests. Pooled sensitivity, specificity, diagnostic odds ratio DOR , and areas under the summary receiver-operating characteristic curves SROC were also calculated.
A total of 14 studies were included in this meta-analysis. The area under the SROC was 0. The authors concluded that these findings indicated that Tc-MIBI scan is a promising diagnostic modality in predicting the malignancy of lung lesions. Treatment stratification depends on immuno-histochemical PD-L1 measurement of biopsy material, an invasive method that does not account for spatio-temporal heterogeneity.
Using a single-domain antibody sdAb , NM, against PD-L1, radiolabeled site-specifically with technetiumm 99mTc for SPECT imaging, these researchers evaluated the safety, radiation dosimetry and imaging characteristics of this radio-pharmaceutical and correlated tumor uptake with PD-L1 immunohistochemistry results. A total of 16 patients mean age of Administered activity was 3. All patients were monitored for adverse events AEs. No drug-related AEs occurred in this study. The mean effective dose was 8. Tracer uptake was observed in the kidneys, spleen, liver and bone marrow. Nodal and bone metastases showed tracer uptake.enter site
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Tumor uptake was readily visible against background tissues, particularly at 2 hours when the T:BP ratio correlated with PD-L1 immunohistochemistry results. Sato and Matsumoto stated that multi-phase arterial spin labeling ASL , which obtains the imaged slices with various post-labeling delays, allows for the non-invasive assessment of cerebral hemodynamics that cannot be adequately acquired by SPECT imaging. These investigators described the clinical usefulness of multi-phase ASL in a patient with symptomatic carotid stenosis by comparison with SPECT at rest using iodo-amphetamine.
The patient underwent stent placement for the left ICA stenosis. The authors concluded that this case showed that multi-phase ASL could accurately evaluate the cerebral hemodynamic status that could not be detected using pre- and post-operative SPECT. Noyce and colleagues examined if pre-diagnostic features of PD were associated with changes in dopamine re-uptake transporter-SPECT and transcranial sonography. The authors concluded that the dopamine re-uptake transporter-SPECT results correlated with motor and non-motor features of pre-diagnostic PD, supporting its potential use as a marker in the prodromal phase of PD; transcranial sonography results also correlated with risk scores and motor signs.
Al-Oweidi and colleagues noted that the prevalence and predictors of myocardial ischemia before non-cardiac surgery are unknown. In addition the predictive value of myocardial perfusion SPECT before non-cardiac in individual patients is uncertain. In a retrospective study, these researchers evaluated the prevalence and predictors of myocardial ischemia before non-cardiac surgery, and determined the post-operative cardiac outcome based on results of myocardial perfusion SPECT. These investigators reviewed the records of adult patients diagnosed with myocardial ischemia by myocardial perfusion SPECT who were undergoing non-cardiac surgery.
Myocardial perfusion SPECT had been performed within 4 weeks prior to non-cardiac surgery requiring general anesthesia. Main outcome measures included prevalence of abnormal myocardial perfusion SPECT results on pre-operative evaluation; abnormal myocardial perfusion SPECT results as a predictor for post-operative cardiac events such as cardiac death, non-fatal MI, and unstable angina. Variables associated with an abnormal myocardial perfusion SPECT included ischemic heart disease, congestive heart failure, American Society of Anesthesiology physical status classification score of 3 or more, limited exercise capacity less than 4 metabolic equivalents [METs] , male sex, hypercholesterolemia, hypertension, smoking, and abnormal ECG.
The authors concluded that because of the low PPV of myocardial perfusion SPECT, utilization of the technique in the work-up of cardiac patients undergoing non-cardiac surgery has been inappropriate. They stated that myocardial perfusion SPECT should be restricted to only clearly defined appropriate use criteria. Falstie-Jensen and colleagues noted that shoulder peri-prosthetic joint infections PJI caused by low-virulent bacteria pose a diagnostic challenge. However, it is laborious and expensive to perform, and documentation on shoulder arthroplasties is lacking. If an arthroplasty was revised, biopsy specimens were obtained and cultured for 14 days.
Related Links. Announcement Information Sheet. Nuclear Medicine. Page Top. Positron emission tomography PET is a nuclear medicine imaging technique that exploits the unique decay physics of positron-emitting radionuclides Sidebar 2. For example, the radiopharmaceutical fluorinefluorodeoxyglucose FDG is a form of sugar labeled with a radionuclide [fluorine] that is imaged using PET.
This imaging technique, which is commonly known as FDG-PET, detects differences between cancer and normal cells in the consumption of glucose. Cancer cells, particularly those from aggressive tumors, proliferate more rapidly than normal cells and consume considerably larger amounts of glucose. Not only can tumor sites be pinpointed through the detection of increased FDG consumption, but differences in FDG consumption in tissues can be detected. In addition, development and regional deployment of lower cost radionuclide-producing machines may make other radiopharmaceuticals based on radionuclides with shorter half-lives such as carbon more widely available.
SPECT uses gamma cameras to obtain three-dimensional images. To acquire SPECT images, the gamma camera is rotated around the patient and multiple images from multiple angles are obtained. A computer can then reconstruct the images. Radiopharmaceuticals used for SPECT are labeled with gamma-emitting radionuclides such as technetiumm, iodine, and thallium SPECT is used extensively to study cardiac health e. Each technique uses different properties of radioactive elements in creating an image.
In addition, the longer half-life of radionuclides used with SPECT makes this imaging procedure more readily available to the medical community at large. However, PET images have higher sensitivity than SPECT images by a factor of 2 to 3 and use radiopharmaceuticals that provide more physiological information. Targeted radionuclide therapy is a form of treatment that delivers therapeutic doses of radiation to malignant tumors by administering a molecule that is labeled with a radionuclide. The radiotherapeutic agent is made of two components: the radionuclide and the carrier that is used to seek out the tumor cells.
Molecular carriers that can be used include, but are not limited to, peptides that seek their corresponding receptors on cells, and monoclonal antibodies that seek out antigens that are similarly expressed on the cells, as shown in the figure.
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The radionuclide that is attached to the carrier molecule can be chosen for specific characteristics, such as type of radiation decay e. To date, two antibody radiopharmaceuticals have been approved by the FDA yttriumibritumomab tiuxetan and iodinetositumomab for the treatment of lymphoma. Figure 2. Based on data from CMS, the use of positron emission tomography PET is growing faster than the use of any other imaging modality.
The use of nuclear medicine procedures will likely continue to rise in the future Table 2. More importantly, the use of nuclear medicine procedures has improved patient care in many ways. Nuclear imaging allows physicians to cost-effectively obtain medical information that would otherwise be unavailable or would require more invasive procedures, such as surgery or biopsy. TABLE 2. FDG-PET has also had a considerable impact in detecting distant metastases and metastatic disease in lymph nodes that appear normal on CT scan e.
For more than 50 years, the AEC and later the Department of Energy DOE have supported high-risk research and development of nuclear medicine technology and have supplied radionuclides to the research community including physicists, chemists, engineers, computer scientists, biologists, and physicians. One of the earliest applications of nuclear medicine was the use of radioactive iodine to treat thyroid cancer.
It also was used to measure thyroid function, diagnose thyroid disease, and treat hyperthyroidism, a condition where the thyroid gland produces excess amounts of thyroid hormones. The significant discoveries in nuclear medicine were made possible by advancements in the basic understanding of biological processes, chemistry, physics, and. Sidebar 2. The output over the past 50 years, as documented in the preceding section, has been extensive.
Although nuclear medicine already contributes to biomedical research and disease management, its promise is only beginning to be realized in areas such as neuroscience, drug development, preventive health care, and other aspects of medicine Sidebar 2. Examples of advances that may be possible from continued multi-disciplinary research and development are discussed in the sections below.
The first section 2. The second section 2. The knowledge gained and the tools developed during the course of the Human Genome Project 2 in addition to several decades of focused biomedical research are revolutionizing medicine. For example, thousands of genetic changes with known biological functions have been discovered and the number will grow as low-cost, next-generation genome analysis technologies are applied.
Omic 3 analyses are revealing differences in DNA, RNA, and protein expression between patients with cancer or heart disease and healthy subjects that can be detected in their blood, urine, feces, and sputum. Current tests are now approaching sensitivity levels that will allow detection of disease at subclinical levels, which is especially important for cancer management. Detection of subclinical disease demands the development of imaging procedures that can accurately pinpoint the location of the diseased tissue so.
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The full sequence was completed in April Omic is an all-encompassing term used to describe comprehensive analyses of molecular or cellular characteristics. Genomics, for example, describes molecular assessment of the entire genome, and proteomics refers to measurement of the proteins found in cells and tissues. Lawrence at the UC Radiation Laboratory later to become the Lawrence Berkeley National Laboratory develops the cyclotron that will produce the first medically useful radionuclides, including iodine, thallium, technetiumm, carbon, and gallium The first reactor-produced radionuclides for medical research are made at Oak Ridge National Laboratory ORNL ; these included phosphorous, iron, and chromium Carbon was first produced and used in biological studies at the University of California at Berkeley by Martin Kamen and colleagues.
Benedict Cassen at the University of California at Los Angeles UCLA invents the first automated scanner to image the thyroid gland after administering radioiodine to patients. Today, technetiumm is used in over 70 percent of nuclear medicine procedures worldwide Nuclear Energy Agency Scientists at ORNL discover the affinity of gallium for soft-tissue tumors. This radionuclide has been used to image lymphomas, lung cancer, and brain tumors.
Hot atom chemistry a work by Alfred Wolf, Michael Welch, and other scientists lays the groundwork for what will become radiopharmaceutical chemistry. The efficient production of thallium is developed by scientists at BNL. This procedure is still used today to assess reduced blood flow or tissue damage to the heart. A new radiopharmaceutical, iodine m-Iodine-benzyl-guanidine I MIBG , is developed by Donald Wieland for the diagnosis and treatment of rare childhood cancers.
Scientists at Harvard Medical School and MIT develop technetiumm-methoxyisobutylnitrile, an agent to measure blood flow to the heart muscle used in myocardial perfusion scans.
Chemists at national laboratories and federally supported academic laboratories developed methods to synthesize high-specific-activity C and Flabeled compounds for imaging neurotransmitter and other physiological activities, laying the foundation for modern molecular imaging. A high-resolution PET scanner designed to image small laboratory animals i.
Scientists at ORNL develop the rhenium generator, which provides hospitals with a ready source of isotopes to treat bone pain in cancer patients. Radionuclides scandium, copper, samarium, rhenium, and gold used in therapeutic nuclear medicine procedures are developed by scientists at multiple national laboratories. Radiolabeled antibodies are developed for therapy see Sidebar 2. Physicians already practice a form of personalized medicine by using diagnostic tests to choose treatment options; however, the wealth of knowledge that is emerging is helping physicians individualize treatment for each patient with greater precision i.
Two examples, the second of which is specific to nuclear medicine, are provided to illustrate this concept. Breast cancer is the most common form of cancer in women, after non-melanoma skin cancer and lung cancer, and approximately , new cases are diagnosed each year CDC There are different types of breast cancer, and they are largely classified and treated on the basis of anatomy i. More recently, with advances in the molecular characterization of the disease, oncologists now recognize that the subtypes of breast cancer are separate diseases that require different biologically based therapies.
One type of breast cancer overexpresses the human epidermal growth factor receptor 2 HER2 receptor. An estimated 25 percent of breast cancer tumors are HER2-positive and these tumors tend to grow and spread more quickly compared with breast cancer tumors that are HER2-negative Herceptin It is thought that trastuzumab stops the cancer cells from growing and dividing, and results from a large international clinical trial showed that the patients who received trastuzumab and chemotherapy were half as likely to have a recurrence of breast cancer as those who received chemotherapy alone Piccart-Gebhard et al.
This drug offers no benefit to patients whose breast cancer tumors do not overexpress HER2. By differentiating the tumors based on molecular differences and targeting these differences, more effective treatment can be delivered to the patient. It is also used to detect residual cancer and to monitor the reduction in tumor. The most exciting area in imaging today and going forward is molecular imaging through various imaging technologies from the laboratory setting to clinical research and practice.
Molecular imaging has become a scientific discipline in its own right, as well as a growing practice in medicine. MRI and optical imaging, as well as nuclear medicine imaging, can be used for molecular targeting. The three approaches differ in sensitivity:. Although its use for monitoring response is only reimbursed by Medicare for certain applications in the management of breast cancer, clinical trials in non-small-cell lung cancer, lymphoma, and esophageal cancer have shown that FDG-PET imaging can predict patient response to treatment. The figure below shows images taken in a lymphoma patient before and after treatment with the radioactively labeled anticancer agent, Zevalin.
The tumor shows intense FDG uptake in the image taken before initiation of treatment. In contrast, the image taken after treatment shows a marked decrease in FDG uptake, indicating a favorable response to therapy. FDG-PET has the potential to improve patient care by allowing treatments with approved medicines to be selected to maximize individual patient response Kelloff et al. MRI probes can be detected at micromolar concentrations, optical probes at picomolar concentrations, and nuclear probes at nanomolar concentrations.
All of these probes can be chemically attached or encapsulated to target specific tissue receptor sites or may be attached to a moiety that preferentially accumulates in a region of interest. Nuclear photons, unlike optical ones, can escape from the body and thus can be used for more deeply seated targets Weissleder It is therefore likely that nuclear. This will require high-specific-activity radiotracers targeted to specific molecular markers as well as imaging devices with greater resolution and sensitivity. The existence of disease subtypes may, in part, explain why similar clinical diagnoses often result in substantially different outcomes in different individuals.
Nuclear medicine may contribute to the management of such diseases by providing information about individual responses to therapy. As illustrated in Sidebar 2. Such monitoring allows earlier determination of the effectiveness of approved treatments in individual patients and, if necessary, enables the patient to start an alternative treatment sooner. It also may facilitate evaluation of the effectiveness of experimental medicines, thereby speeding their entry into clinical practice while reducing cost.
Other current as well as next-generation nuclear medicine procedures will similarly accelerate the delivery of personalized care to the patient. Nuclear medicine imaging will enable functional investigations of numerous aspects of normal and abnormal physiologies. These include, but are not limited to, neurotransmitter activity, chemical determinants of behavior, neurodegeneration, immune response, remodeling of heart tissue, and bone metabolism. Imaging of specific carbonlabeled agents to assess brain function is possible, but increasingly, fluorinelabeled compounds such as FDG, fluorinedihydroxyphenylalanine, and fluorinelabeled fallypride 4 are being used to assess brain degeneration and cognitive function.
Improvements in imaging instruments that have greater spatial and temporal resolution and radiotracers with high specific activities will allow more precise non-invasive assessment of these physiological functions. In many cases, this will require imaging of low concentrations of proteins.
Fallypride is a chemical compound i. Dopamine receptors have a role in processes such as motor and learning.
Single Photon Emission Computed Tomography (SPECT)
To achieve this, new technologies will need to be developed that can produce these short-half-life radionuclides cost-effectively at many sites distributed around the country Section 2. Currently, they are available in research settings where a cyclotron and chemists are nearby. This wealth of targets and therapeutic agents bodes well for individualized disease management. However, capitalizing on these developments requires years of work and considerable financial commitment.
In part, this is because only one in five drugs that enter clinical trials actually proceeds to an approval stage Wierenga and Eaton , and many drugs fail in the late stages of clinical testing i. Moreover, the time line for bringing a new drug to clinical use takes, on average, 12 years Wierenga and Eaton The time and expense required to bring a drug to market may be reduced by using nuclear medicine imaging technologies to identify which drugs should advance from animal to human studies, reveal mechanisms of drug action, evaluate drug distribution to target tissue; establish the drug occupancy of receptor sites; assess the actions of new agents on specific molecular targets or pathways; and determine appropriate dose range and regimen Eckelman The overall approach will bring together the strengths of these three agencies and the pharmaceutical industry to determine the optimum use of biomarkers to evaluate treatment response.
Clearly, radiotracers are likely to be excellent biomarkers. A clinical trial is a research study conducted in human volunteers that is designed to answer specific questions.
There are different types of clinical trials, such as treatment, prevention, diagnostic, and screening trials, each of which answers a different question. Treatment trials are the most common, and clinical trials are conducted in phases, where each phase has a different purpose. Phase I trials: An experimental drug or treatment is given to a small group of patient volunteers usually between 20 and 80 to evaluate its safety, determine a safe dosage range, and identify side effects.