PET/CT assessment in follicular lymphoma using standardized criteria: central review in the PRIMA study

Purpose

We aimed to compare the standardized central review of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans performed after induction therapy for follicular lymphoma (FL) in the PRIMA study (Salles et al., Lancet 377:42–51, 2011; Trotman et al., J Clin Oncol 29:3194–3200, 2011) to scan review at local centres.

Methods

PET/CT scans were independently evaluated by two nuclear medicine physicians using the 2007 International Harmonization Project (IHP) criteria (Cheson et al., J Clin Oncol 25:579–586, 2007; Juweid et al., J Clin Oncol 25:571–578, 2007; Shankar et al., J Nucl Med 47:1059–1066, 2006) and Deauville 5-point scale (5PS) criteria (Meignan et al., Leuk Lymphoma 50:1257–1260, 2009; Meignan et al., Leuk Lymphoma 51:2171–2180, 2010; Barrington et al., Eur J Nucl Med Mol Imaging 37:1824–1833, 2010). PET/CT status was compared with prospectively recorded patient outcomes.

Results

Central evaluation was performed on 119 scans. At diagnosis, 58 of 59 were recorded as positive, with a mean maximum standardized uptake value (SUV_max) of 11.7 (range 4.6–35.6). There was no significant association between baseline SUV_max and progression-free survival (PFS). Sixty post-induction scans were interpreted using both the IHP criteria and 5PS. Post-induction PET-positive status failed to predict progression when applying the IHP criteria [p?=?0.14; hazard ratio (HR) 1.9; 95 % confidence interval (CI) 0.8–4.6] or 5PS with a cut-off ≥3 (p?=?0.12; HR 2.0; 95 % CI 0.8–4.7). However, when applying the 5PS with a cut-off ≥4, there was a significantly inferior 42-month PFS in PET-positive patients of 25.0 % (95 % CI 3.7–55.8 %) versus 61.4 % (95 % CI 45.4–74.1 %) in PET-negative patients (p?=?0.01; HR 3.1; 95 % CI 1.2–7.8). The positive predictive value (PPV) of post-induction PET with this liver cut-off was 75 %. The 42-month PFS for patients remaining PET-positive by local assessment was 31.1 % (95 % CI 10.2–55.0 %) vs 64.6 % (95 % CI 47.0–77.6 %) for PET-negative patients (p?=?0.002; HR 3.3; 95 % CI 1.5–7.4), with a PPV of 66.7 %.

Conclusion

We confirm that FDG PET/CT status when applying the 5PS with a cut-off ≥4 is strongly predictive of outcome after first-line immunochemotherapy for FL. Further efforts to refine the criteria for assessing minimal residual FDG uptake in FL should provide a reproducible platform for response assessment in future prospective studies of a PET-adapted approach.     

The iliac crest in forensic age diagnostics: evaluation of the apophyseal ossification in conventional radiography

Due to the increasing significance of forensic age estimations in the age of globalisation, novel radiographic criteria besides clavicles and hand bones may provide additional certainty for forensic age expertises. The present study analyses the suitability of the iliac crest apophysis by means of 643 pelvic radiographs of patients between 10 and 30 years of age. Retrospective assessments were carried out according to the forensically established classification and sub-classification systems modified after Kreitner et al. (Rofo 166(6):481–486, 1997) and Kellinghaus et al. (Int J Legal Med 124(4):321–325, 2010). The basic ossification stages range from 1 to 4, and the sub-stages of stage 2 and 3 range from a to c. While stage 3c was first achieved at the age of 15 by both sexes, stage 4 was first observed in females at the age of 16 and in males at the age of 17. This indicates the possibility of a valid diagnosis of both the age of 14 and the age of 16 years which represent legally relevant age thresholds in numerous countries. Applied as targeted radiography on the iliac crest, the exposure to radiation would range between other radiographic techniques recently applied. Therefore, the iliac crest apophysis appears principally suitable as novel possible criterion for forensic age estimation in the living. However, for the establishment of the iliac crest apophysis in routine diagnostics, further studies are needed focussing on the comparison of different grading systems and different radiological techniques.     

Brainstem swelling and noncommunicating hydrocephalus caused by hypertensive brainstem encephalopathy

Hypertensive encephalopathy is a life-threatening medical condition manifested by headache, confusion, seizures, and visual disturbance, and, if treatment is delayed, it may progress to coma and death [1, 2] (Chester et al., Neurology 28:928–939, 1978; Vaughan and Delanty, Lancet 356:411–417, 2000). Involvement of the brainstem with or without supratentorial lesions has been reported and is termed hypertensive brainstem encephalopathy (HBE). Cases of HBE involving supratentorial deep gray and white matter are rare and extensive hyperintensity was predominantly seen in brainstem regions on fluid-attenuated inversion recovery and T2-weighted magnetic resonance images. We present radiologic findings of a patient with HBE involving deep supratentorial gray and white matter, causing tonsillar herniation and noncommunicating hydrocephalus by mass effect.     

Bradycardia Associated With Drug-Eluting Beads Loaded With Irinotecan (DEBIRI) Infusion for Colorectal Liver Metastases

Intra-arterial injection of drug-eluting beads loaded with irinotecan (DEBIRI) is a new treatment option being investigated, with encouraging results, for unresectable colorectal liver metastases that are refractory to systemic chemotherapy (Martin et al., Ann Surg Oncol 18:192–198, 2011). Toxicity related to DEBIRI has also been described (Martin et al., Cardiovasc Intervent Radiol 33:960–966, 2010). Nevertheless, experience and literature related to DEBIRI remain limited, and experience with this treatment is expected to increase. The purpose of this article is to describe bradycardia occurring during DEBIRI administration, which has not been reported thus far.     

Respiratory infection in the AIDS and immunocompromised patient

Immunocompromised patients are susceptible to infections by a wide range of organisms. In the past several decades, AIDS epidemic, advances in the treatment of cancer, organ transplantation, and immunossupresive therapy have resulted in large numbers of patients who develop abnormalities in their immune system [1, 2, 3, 4]. Moreover, mildly impaired host immunity as it occurs in chronic debilitating illness, diabetes mellitus, malnutrition, alcoholism, advanced age, prolonged corticosteroid administration, and chronic obstructive lung disease have also been regarded as predisposing factors of pulmonary infections [5]. Imaging plays a crucial role in the detection and management of patients with pulmonary infectious diseases. When pulmonary infection is suspected, knowledge of the varied radiographic manifestations will narrow the differential diagnosis, helping to direct additional diagnostic measures, and serving as an ideal tool for follow-up examinations. Combination of pattern recognition with knowledge of the clinical setting is the best approach to pulmonary infection occurring in the immunocompromised patients.     

Synovial hemangioma of the hip joint in a pediatric patient

Hemangiomas of the articular synovium are rare and commonly associated with recurrent joint swelling and painful limitation of motion. The knee joint is the most commonly involved site, with most patients diagnosed in the second to third decade of life [1]. Although over 200 cases have been reported in the English-language medical literature, only three have originated within the hip joint, all of which were in adult patients reported in the surgical literature [2–4]. We describe a histologically proven synovial hemangioma of the hip joint in a pediatric patient that invaded the femur, acetabulum, and adjacent soft tissues, with a detailed discussion of the differential diagnosis based on the radiographic and magnetic resonance imaging (MRI) findings.     

EANM procedure guidelines for brain neurotransmission SPECT using 123I-labelled dopamine transporter ligands, version 2

These guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aim of the guidelines is to assist nuclear medicine practitioners when making recommendations, performing, interpreting, and reporting the results of clinical dopamine transporter (DAT) single photon emission computed tomography (SPECT) studies using ¹²³I-labelled radiopharmaceuticals. The aim is to achieve a high-quality standard of DAT SPECT imaging, which will increase the diagnostic impact of this technique in neurological practice. The present document is an update of the 2002 guidelines [1] and has been guided by the views of various national societies: the Task Group Neuro-Nuclear-Medicine of the German Society of Nuclear Medicine [2], a consensus statement of the imaging centres included in the “Kompetenznetz-Parkinson” sponsored by the German Federal Ministry of Education, and the Task Group of Neuro-Nuclear-Medicine of the French Society of Nuclear Medicine [3]. The guidelines reflect the individual experience of experts in European countries. The guidelines are intended to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.     

Optimal age classification of young individuals based on dental evidence in civil and criminal proceedings

Background

Criminal cases involving young people, irregular immigration and the many issues related to asylum seekers has increased the judicial demand of age estimation. Calcification of teeth and specifically of third molar has demonstrated to be reliable evidence to estimate age respect to 18 years threshold of age.

Aims

As prosecution of research of Pinchi et al. (2010) and Corradi et al. (J Forensic Sci 58:51–59, 2013), the study aims to evaluate if tuning the size of the zone of indifference posed around the age threshold improves the performances of the age classification model.

Materials and methods

The sample was composed of 1,560 OPGs of Italian subjects aged between 15 and 22 years. Third molar calcification stage was assessed according to Demirjian’s scale by three different experts. Intra- and inter-operator variability has been calculated. The statistical analysis was provided by a Modified Naïve Bayesian allowing the use of soft evidence. Rate of in/correct classification was provided for individuals classified at a very high level of probability (90 %), as needed for criminal cases, and for a lower probability level (51 %) as it suffices for civil cases.

Results

The intra-observer reproducibility varies between 79.2 and 89.2 % with soft evidence, whilst it decreases from values between 0.589 and 0.763, when only hard evidence is allowed to experts showing the usefulness of the MBN approach. In civil cases, imposing the constraint of classifying at least 95 % of the individuals, the method achieved a rate of correct classification in the range 80–83 % depending on the expert. In criminal cases, we tuned the ZOI size to achieve 85 % of individuals correctly classified and the model succeeded in classifying 66–81 % of the sample, the variability still being dependent on the expert’s ability.

Conclusions

After a review of several studies concerning the age classification of young individuals by using dental evidence, we must conclude that it is almost impossible to make a comparison among them. To rank the effectiveness of different methods is to challenge them with the same problem and data, looking at the results measured by the same accepted scoring rule. It could also be interesting to repeat the experiment in different conditions varying the reference population and considering if some important covariates, like sex and health status, influence the model performances.     

Pairwise comparison of 89Zr- and 124I-labeled cG250 based on positron emission tomography imaging and nonlinear immunokinetic modeling: in vivo carbonic anhydrase IX receptor binding and internalization in mouse xenografts of clear-cell renal cell carcinoma

Purpose

The PET tracer, ¹²⁴I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304–310, 2007; Divgi et al. in J Clin Oncol 31:187–194, 2013). The radiometal ⁸⁹Zr, however, may offer advantages as a surrogate PET nuclide over ¹²⁴I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265–282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between ¹²⁴I-cG250 and ⁸⁹Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody–antigen binding and turnover.

Methods

We conducted experiments with ⁸⁹Zr-cG250 and ¹²⁴I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling.

Results

The two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using ⁸⁹Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 – 5.51?×?10¹² molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of ¹²⁴I/⁸⁹Zr atoms released per unit time by tumor was 17.5.

Conclusion

Pairwise evaluation of ⁸⁹Zr-cG250 and ¹²⁴I-cG250 provided the basis for a nonlinear immunokinetic model which yielded quantitative information about the binding and internalization of radioantibody bound to CAIX on tumor cells in vivo. ⁸⁹Zr-cG250 is likely to provide high-quality PET images and may be a useful tool to quantify CAIX/cG250 receptor turnover and cG250-accessible antigen density noninvasively in humans.     

Der stereoselektive Nachweis von l- und d-Methadon in Blutproben von lebenden und verstorbenen Drogenabhängigen

In Germany, there is a special situation that racemic dl-methadone and the (biologically effective) l-form (levomethadone) are both used as a substitute for heroin. The therapeutic effect of methadone is stereo-specific and the metabolism is also enantioselective. Therefore an approach to the dose-effect relationship of methadone requires an enantioselective analytical separation. For this a HPLC method was optimised especially for post-mortem blood samples. After liquid/¶liquid extraction with 1-chlorobutane, the extract was separated on a column combination of 4 cm CN and 10 cm chiral AGP phases with the solvent AcN/ 0.01 M PO₄ buffer ¶pH 5.0/ dimethyloctlyamine (15/85/0.5). ¶The methadone enantiomers elute baseline separated at approx. 15 min (l-form) and ¶18 min (d-form). The two EDDP-enantiomers and drugs which are frequently consumed supplementary to methadone such as heroin, cocaine, benzodiazepines, tricyclic antidepressants, antiepileptics etc. , do not interfere with detection. With this method the methadone l/d-ratio was determined in 93 serum samples from living addicts and 106 post-mortem blood samples from drug deaths. From the l/d-ratio and the concentration of total methadone as determined by other methods (GC-MS or RP-HPLC) the l-methadone concentration was calculated. In approximately 50% of the post-mortem samples the l-methadone concentration was higher than 0.3 mg/l, whereas this level was exceeded in only one of the living persons. ¶If dl-methadone was taken, the individual l/d-ratio in blood samples from living as ¶well as deceased persons differed greatly ranging from approx. 25/75 to 75/25, with ¶a mean of 50/50. In samples from 1999, ¶l-methadone was found exclusively in approx. 20% of the cases. In some cases it was obvious that both l- and dl-methadone had been used. Fatal cases with high l-methadone concentrations (>1 mg/l) gave rise to concern, because the l/d-ratio greatly exceeded 50/50in all cases . This could be considered as an indication of an individually extremely slow metabolism of l-methadone in these cases, resulting in an accumulation of l-methadone. These examples from the forensic casework demonstrate the necessity of an enantioselective quantification of ¶l-methadone as used for therapeutic drug monitoring and in forensic cases.     

The role of myocardial perfusion imaging in evaluating patients with myocardial bridging

Background

Myocardial bridging (MB) is a common, congenital coronary-abnormality that is found on average in one out of every three adults at autopsy (Moehlenkamp et al in Circulation, 106:2616-2622, 2002; Erbel et al in Circulation, 120:357-359, 2009). However, its clinical significance and impact on myocardial ischemia remains controversial and unclear. Myocardial perfusion imaging (MPI) is widely used to assess myocardial ischemia in patients with known or suspected coronary artery disease, and is frequently performed to evaluate the hemodynamic significance of MB. This study was undertaken to determine the use of MPI in evaluating MB and to identify the characteristics of MB associated with perfusion defects using MPI.

Methods and Results

Thirty-nine patients with MB of the left anterior descending (LAD) artery as documented by coronary angiography (CA) were enrolled for this study. None of the patients exhibited other forms of heart disease as determined by both CA and stress-rest MPI, no later than 1 month prior to the study. Using MPI, eight patients (20.5%) were found to have perfusion defects in the corresponding myocardial areas. This frequency was significantly higher when compared with results obtained by stress electrocardiogram. The difference in the mean systolic narrowing of bridging segments was statistically significant between patients with and without ischemia. The positive rate of reversible defects in patients with severe systolic narrowing was significantly higher than in patients with mild-to-moderate systolic narrowing. However, there was no significant difference either between the mean length of the tunneled artery in patients with and without abnormal MPI or the positive rate of abnormal MPI in patients with different locations of the tunneled artery.

Conclusions

MPI is an effective, noninvasive technique for the evaluation of patients with MB. The myocardial ischemia that resulted from bridging is associated more closely with the degree of systolic narrowing than with the length of tunneled artery or the location of MB.     

EANM procedure guidelines for brain neurotransmission SPECT/PET using dopamine D2 receptor ligands, version 2

The guidelines summarize the current views of the European Association of Nuclear Medicine Neuroimaging Committee (ENC). The aims of the guidelines are to assist nuclear medicine practitioners in making recommendations, performing, interpreting and reporting the results of clinical dopamine D2 receptor SPECT or PET studies, and to achieve a high quality standard of dopamine D2 receptor imaging, which will increase the impact of this technique in neurological practice. The present document is an update of the first guidelines for SPECT using D2 receptor ligands labelled with ¹²³I [1] and was guided by the views of the Society of Nuclear Medicine Brain Imaging Council [2], and the individual experience of experts in European countries. The guidelines intend to present information specifically adapted to European practice. The information provided should be taken in the context of local conditions and regulations.     

Transhemangioma Ablation of Hepatocellular Carcinoma

Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.     

Medical imaging, PACS, and imaging informatics: retrospective

Historical reviews of PACS (picture archiving and communication system) and imaging informatics development from different points of view have been published in the past (Huang in Euro J Radiol 78:163–176, 2011; Lemke in Euro J Radiol 78:177–183, 2011; Inamura and Jong in Euro J Radiol 78:184–189, 2011). This retrospective attempts to look at the topic from a different angle by identifying certain basic medical imaging inventions in the 1960s and 1970s which had conceptually defined basic components of PACS guiding its course of development in the 1980s and 1990s, as well as subsequent imaging informatics research in the 2000s. In medical imaging, the emphasis was on the innovations at Georgetown University in Washington, DC, in the 1960s and 1970s. During the 1980s and 1990s, research and training support from US government agencies and public and private medical imaging manufacturers became available for training of young talents in biomedical physics and for developing the key components required for PACS development. In the 2000s, computer hardware and software as well as communication networks advanced by leaps and bounds, opening the door for medical imaging informatics to flourish. Because many key components required for the PACS operation were developed by the UCLA PACS Team and its collaborative partners in the 1980s, this presentation is centered on that aspect. During this period, substantial collaborative research efforts by many individual teams in the US and in Japan were highlighted. Credits are due particularly to the Pattern Recognition Laboratory at Georgetown University, and the computed radiography (CR) development at the Fuji Electric Corp. in collaboration with Stanford University in the 1970s; the Image Processing Laboratory at UCLA in the 1980s–1990s; as well as the early PACS development at the Hokkaido University, Sapporo, Japan, in the late 1970s, and film scanner and digital radiography developed by Konishiroku Photo Ind. Co. Ltd. (Konica-Minolta), Japan, in the 1980–1990s. Major support from the US National Institutes of Health and other federal agencies and private medical imaging industry are appreciated. The NATO (North Atlantic Treaty Organization) Advanced Study Institute (ASI) sponsored the International PACS Conference at Evian, France, in 1990, the contents and presentations of which convinced a half dozen high-level US military healthcare personnel, including surgeons and radiologists, that PACS was feasible and would greatly streamline the current military healthcare services. The impact of the post-conference summary by these individuals to their superiors opened the doors for long-term support of PACS development by the US Military Healthcare Services. PACS and imaging informatics have thus emerged as a daily clinical necessity.     

Bulgarians vs the other European populations: a mitochondrial DNA perspective

To define the matrilineal relationships between Bulgarians and other European populations, we have evaluated the mitochondrial DNA (mtDNA) variation in a sample of 855 Bulgarian subjects from the mtDNA perspective. The molecular survey was performed by sequencing ～750?bp of the control region, which resulted in 557 different haplotypes, and by a subsequent restriction fragment length polymorphism analysis to confirm haplogroup/subhaplogroup affiliation. The classification was carried out according to the most updated criteria as reported by van Oven and Kayser (Hum Mutat 30:386–394, 2009), allowing the identification of 45 mitochondrial clades. The observed pattern of mtDNA variation indicates that the Bulgarian mitochondrial pool is geographically homogeneous across the country, and that is characterized by an overall extremely high frequency of western Eurasian lineages. In the principal component analysis, Bulgarians locate in an intermediate position between Eastern European and Mediterranean populations, which is in agreement with historical events. Thus, while the Mediterranean legacy could be attributed to the Thracians, indigenous people that firstly inhabited the Balkans, the Eastern contribution is likely due to the Proto-Bulgarians originating from the Middle East and to the Slavs migrating from northeast Europe.     

Open versus arthroscopic surgical treatment of chronic proximal patellar tendinopathy. A systematic review

Purpose

A general agreement on the best surgical treatment option of chronic proximal patellar tendinopathy is still lacking. The purpose of this systematic review was to investigate if arthroscopically assisted procedures have been reported better results compared to open surgery and to assess the methodology of studies.

Methods

Twenty-one studies were included in the review. Surgical outcomes were defined referring to the functional classification described by Kelly et al. (Am J Sports Med 12(5):375–380, [11]): return to sport was regarded as the ability of training at the original level before injury with mild or moderate pain and success as the improvement after surgery with symptom reduction. Methodological analysis was performed by two reviewers adopting the Coleman Methodology Score (CMS) (range 0–100, best score 100).

Results

Only one randomized controlled trial (RCT) met inclusion criteria; all other included studies were case series. Median sample size 24, range 11–138, mean age at surgery 26.8 ± 3.2 years, mean follow-up 32.5 ± 18.4 (median 31, range 6–60) months. Return to sport rate: global 78.5 %, open group 76.6 % and arthroscopic group 84.2 %. Success rate: global 84.6 %, open group 87.2 % and arthroscopic group 92.4 %. Differences between groups were not statistically significant. CMSs were positively correlated with the year of publication (P < 0.05).

Conclusions

Minimally invasive arthroscopically assisted procedures have not reported better statistically significant results when compared to open surgery in the treatment of chronic proximal patellar tendinopathy. The methodology of studies in this field has improved over the past 15 years, but well-designed RCTs using validated patient-based outcome measures are still lacking.

Level of evidence

Systematic Review, Level IV.     

A Paper About a Piece of Paper

The only constant is change. Heraclitus 1 ¹ See Geoffrey Stephen Kirk et al., The Presocratic Philosophers: A Critical History with a Selection of Texts 186–87 (1957).

It strikes me that the questions brought on by medical technology have come upon us in a relatively short time, and that society is at the beginning of even grasping their dimension and complexity, let alone coming up with satisfactory answers.

William H. Colby 2 ² William H. Colby, Unplugged: Reclaiming Our Right to Die in America 95 (2006). Colby was the attorney for the family of Nancy Cruzan, whose end-of-life decision-making case was the first one heard in the United States Supreme Court. Cruzan v. Dir., Mo. Dep't of Health, 497 U.S. 261 (1990).      

The effect of 18F-florbetapir dose reduction on region-based classification of cortical amyloid deposition

?

There are specific dose recommendations for diagnostic amyloid PET imaging with 18F-florbetapir, but they may not apply to research studies using regional quantitative analysis. We, therefore, studied the effect of tracer dose reduction on the discriminative power of regional analysis.

Methods

Using bootstrap resampling of list-mode data from 18F-florbetapir scans, a total of 800 images were reconstructed for four different dosage levels: 100, 50, 20, and 10 %. The effect of the injected dose on the variation of measured radiotracer uptake was determined in large cortical regions defined on co-registered and segmented magnetic resonance images. The impact of the observed variation on the discrimination between normal controls and patients with AD was then assessed using data in a cohort study described by Fleisher et al. (Arch Neurol 68(11):1404–1411, 2011).

Results

The coefficient of variance for the cortex to cerebellum uptake ratio increased from 0.9 % at full dose of 300 MBq to 2.5 % at 10 % of this dose, but was still small compared to biological variation. It, therefore, had very little impact on discrimination between AD and elderly controls. The original area under the ROC curve was 0.881, decreasing to 0.878 at 10 % of full dose. Original sensitivity for discrimination between AD and controls was 82.0 %, while specificity was 77.3 %; these decreased to 81.8 and 77.1 %, respectively, at the reduced dose. However, the number of subjects within the classification border zone between proven amyloid pathology and young healthy controls increased substantially by 7 to 14 %.

Conclusion

A substantial reduction of tracer dose increases uncertainty at the classification border zone while still providing good discrimination between AD patients and controls when using activity data from cortical regions defined on co-registered and segmented MR scans.     

Stellungnahme zur Studie „Cannabis im Straßenverkehr”

In his recent study “Cannabis im Straßenverkehr” Prof. Dr. Th. Daldrup was searching for reliable criteria assessment of drivers’ incapacity after Cannabis use. He proposed the “Cannabis influence factor” (CIF) as a measure of impairment of driving performance. The CIF is calculated from the formula: $$CIF = \frac{{\left( {THC + 11 - OH - THC} \right)}}{{THC - COOH \times 0.01}}$$ after determination of all analytes in blood (in molar concentration). A CIF value above 10 was said to be equivalent to an absolute incapacity to drive (like BAC of 1.1 g/l). The conclusions of the study, especially the immediate forensic use of CIF as a “cut-off value” for impaired driving, are not supported by the data presented and are questionable from the pharmacokinetical and methodological points of view. The forensic application of various combinations of analytical data as a measure of drivers’ performance after cannabis use obviously needs further, intensive study.