Janet C. Miller

Clinical molecular imaging.

This review summarizes the rapidly growing field of molecular imaging, the spatially localized and/or temporally resolved sensing of molecular and cellular processes in vivo. Molecular imaging is used to map the anatomic locations of specific molecules of interest within living tissue and has enormous potential as a powerful means to diagnose and monitor disease. Molecular imaging agents comprise a targeting component that confers localization and a component that enables external detectability with an imaging modality, such as PET, SPECT, MRI, optical, and ultrasound. The advantages and disadvantages of each of these modalities are discussed in regard to spatial resolution, temporal resolution, sensitivity, and cost. Molecular imaging agents can be divided into three categories, Type A, which bind directly to a target molecule, Type B, which are accumulated by molecular or cellular activity by the target, and Type C, which are undetectable when injected but can be imaged after they are activated by the target. The current status of clinical molecular imaging agents is presented as well as examples of some preclinical applications. The value of molecular imaging is illustrated by some examples for diseases such as cancer, neurological and psychiatric disorders, cardiovascular disease, infection and inflammation, and the monitoring of gene therapy and stem cell therapy.

Globalization of P4 Medicine: Predictive, Personalized, Preemptive, and Participatory—Summary of the Proceedings of the Eighth International Symposium of the International Society for Strategic Studies in Radiology, August 27–29, 2009

In August 2009, the International Society for Strategic Studies in Radiology held its eighth biennial meeting. The program focused on the globalization of predictive medicine--or P4 medicine--as it relates to the practice of radiology and radiology research. P4 medicine refers to predictive, personalized, preemptive, and participatory medicine and was the inspiration of Elias Zerhouni, MD, former director of the National Institutes of Health. This article is a summary of some of the key concepts presented at the meeting by an international group of radiologists, imaging scientists, and leaders of industry. In predictive medicine, imaging and imaging-related technologies will likely play an increasing role in the early detection of disease and, thus, the preemption of the development of advanced, hard-to-treat disease. Research into systems biology and molecular imaging promises to personalize medicine, facilitating the provision of the right care to the right patient at the right time. In participatory medicine, increasing interactions with referring physicians and patients will be helpful in raising awareness and recognition of the role of radiologists and will have a positive effect on professionalism. There is also a need to increase awareness of the vital role of radiologists as imaging and radiation safety experts who evaluate the necessity and appropriateness of examinations, monitor performance quality, and are available for postexamination consultations.

Integrated diagnostics: proceedings from the 9th biennial symposium of the International Society for Strategic Studies in Radiology

AbstractThe International Society for Strategic Studies in Radiology held its 9th biennial meeting in August 2011. The focus of the programme was integrated diagnostics and massive computing. Participants discussed the opportunities, challenges, and consequences for the discipline of radiology that will likely arise from the integration of diagnostic technologies. Diagnostic technologies are increasing in scope, including advanced imaging techniques, new molecular imaging agents, and sophisticated point-of-use devices. Advanced information technology (IT), which is increasingly influencing the practice of medicine, will aid clinical communication and the development of “population images” that represent the phenotype of particular diseases, which will aid the development of diagnostic algorithms. Integrated diagnostics offer increased operational efficiency and benefits to patients through quicker and more accurate diagnoses. As physicians with the most expertise in IT, radiologists are well placed to take the lead in introducing IT solutions and cloud computing to promote integrated diagnostics. To achieve this, radiologists must adapt to include quantitative data on biomarkers in their reports. Radiologists must also increase their role as participating physicians, collaborating with other medical specialties, not only to avoid being sidelined by other specialties but also to better prepare as leaders in the selection and sequence of diagnostic procedures. Key Points • New diagnostic technologies are yielding unprecedented amounts of diagnostic information.• Advanced IT/cloud computing will aid integration and analysis of diagnostic data.• Better diagnostic algorithms will lead to faster diagnosis and more rapid treatment.

Functional CT and MR Imaging for Evaluation of Acute Stroke

When a patient arrives with symptoms of stroke, prompt imaging is a vital part of the work-up. For patients with ischemic stroke, thrombolytic therapy with intravenous tissue plasminogen activator (t-PA) must be given within the first 3 hours and intra-arterial thrombolytic therapy must be administered within 6 hours after the onset of symptoms to be effective. Late therapy limits the efficacy of treatment and increases the likelihood of brain edema and hemorrhage, which may be life threatening. Therefore, the potential benefits of recanalization must be weighed against the risks of increased morbidity and mortality. CT and MR imaging now play a significant role not only for diagnosis but also for assessing the volume of ischemic damage and amount of residual perfusion. This data, although still under investigation, plays a role in decision making on whether it is appropriate to give the patient thrombolytic treatment.

Screening for Hepatocellular Carcinoma in Cirrhotic Patients

The incidence of hepatocellular carcinoma (HCC) has increased dramatically in the United States within recent decades [1], and it is now the fourth leading cause of cancer-related deaths worldwide [2]. The increase has been driven mainly by the epidemic of hepatitis C virus infection. The 5-year cumulative risk for developing HCC is 17% for persons with hepatitis C virus cirrhosis [3]. However, all causes of cirrhosis increase the risk, and patients with cirrhosis have an annual risk of 1% to 6% for developing HCC [4]. Nonalcoholic steatohepatitis, which is associated with type 2 diabetes and obesity, also seems to be associated with an increased risk for developing HCC [5]. However, about 90% of all cases are found in patients who are cirrhotic [3], and in the United States, HCC is most commonly found in men aged 45 to 65 years [1].

The relationship between the incorporation of 32P into phosphatidic acid and phosphatidylinositol in rat parotid acinar cells.

Abstract Muscarinic and α-adrenergic stimulation of rat parotid acinar cells increases the turnover of phosphatidylinositol and phosphatidic acid. It is thought that this is initiated by hydrolysis of phosphatidylinositol, which would predict an increase in 32 P incorporation into phosphatidic acid before phosphatidylinositol. We have demonstrated an increase in 32 P incorporation into the former within 1 minute and into the latter by 2 minutes. The initial rapid rate of 32 P incorporation into phosphatidic acid slows, and the 32 P content reaches a steady state after 15 minutes. During the first 2 minutes after the addition of atropine to carbamylcholine stimulated cells, 32 P is lost from phosphatidic acid, and an equal amount is gained by phosphatidylinositol, after which 32 P incorporation equals that of the control. In cells prelabelled with 32 P, carbamylcholine, in the presence of oligomycin stimulated the loss of 32 P from phosphatidylinositol but had no effect on phosphatidic acid.

Dual-Source CT for Cardiac Imaging

F g 7 he constant motion of the heart and he small size of coronary arteries resent a considerable challenge in he acquisition of diagnostic-quality mages. Fast multidetector computed omographic (CT) scanners and ated cardiac imaging overcame many f thecardiacmotionchallenges.Howver, even with 64-detector scanners, it as not possible to obtain diagnosticuality images in many patients with eart rates greater than 65 beats per inute because of distortions from yocardial motion. A solution was to dminister -blockers before imaging o lower the heart rate [1]. However, his was not always possible, nor was it ffective in some patients. Furtherore, because some of the reconstrucion methods combined data from sevral consecutive cardiac cycles, it was ot possible to image patients with sigificant heart rate variability.

Ultrasound and Sonohysterography in the Evaluation of Abnormal Vaginal Bleeding

Although most abnormal vaginal bleeding is caused by hormone imbalance, it can be indicative of disease, including endometrial polyps and hyperplasia, and cancers of the cervix and endometrium [1]. In postmenopausal women, the greatest concern is endometrial cancer, which is now the most common gynecologic cancer in the United States. Because this is curable if detected early, it is important to determine the cause of all cases of postmenopausal vaginal bleeding to avoid missed diagnoses of endometrial cancer. More than 90% of the cases of endometrial cancer occur in women older than 50 years of age, and this disease accounts for approximately5%ofthecasesofvag

Effects of pentobarbital and veratridine on phosphatidylinositol and phosphatidate metabolism in rat parotid acinar cells

The metabolism of phosphatidylinositol and phosphatidate was studied in isolated rat parotid cells, incubated in a physiological buffer containing [32P]phosphate or [3H]glycerol. Carbamylcholine and epinephrine stimulated 32P incorporation into both of these phospholipids, causing their half-maximal effects at 2 and 0.8 microM respectively. The former concentration is much lower than that anticipated from binding studies. The Hill coefficients for carbamylcholine activation of 32P incorporation were 0.61 +/- 0.05 for phosphatidate and 0.64 +/- 0.05 for phosphatidylinositol. Pentobarbital (0.58 mM) inhibited the increased 32P incorporation caused by 5 microM carbamylcholine but not 100 microM carbamylcholine. Pentobarbital inhibited the incorporation of 3H equally in the presence and absence of epinephrine, indicating that the effect of pentobarbital on 32P incorporation is on turnover and not on de novo synthesis. Veratridine (200 microM) had no effect on phospholipid metabolism in the presence and absence of either carbamylcholine or epinephrine, which contrasts with our previous findings in synaptosomes [J.C. Miller and I. Leung, Biochem. J. 178, 9 (1979)].

Imaging Biomarker Applications in Oncology Drug Development

At present, drug development is a long and costly process with an unacceptably high failure rate. As a result, both the Food and Drug Administration and the pharmaceutical industry have shown interest in using biomarkers of clinical response. Biomarker imaging is noninvasive, allows serial data collection, and lessens interpatient variability because each individual can serve as his or her own control. The only imaging biomarker currently accepted as a surrogate for clinical response is tumor shrinkage for accelerated approval. The imaging biomarker, 18F-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET), is widely used clinically to assess response to therapy and, in some cases, correlates better with prolonged survival than tumor shrinkage. Other biomarkers, such as hemodynamic biomarkers, have been used in early clinical trials as a means to assess bioactivity within hours or days of the start of treatment and to determine drug dose in subsequent trials. Many others have found applications in assessing bioactivity in preclinical stages of drug development. With further validation, many of these imaging biomarkers could become valuable in measuring response to therapy much faster than present methods. In addition, pharmacokinetic imaging will provide both clinical and preclinical data on uptake, distribution, and excretion of drug candidates.