An audit of local discrepancy rates in acute abdominal CT: does subspecialist reporting reduce discrepancy rates?

AIM: To assess the discrepancy rates (DR) for patients undergoing abdominopelvic computed tomography (CT) for acute non-traumatic abdominal pain who have a subsequent emergency laparotomy in a large university teaching hospital, in particular identifying the differences between subgroups of reporters, to assess factors that may influence the discrepancy rates, to examine the pathologies with the highest discrepancy rate, to identify learning points, and give recommendations on current practice. MATERIALS AND METHODS: The surgical data and CT reports of 1,176 patients who underwent urgent laparotomy after CT from 2014-2018 in a large university hospital were analysed retrospectively. A major discrepancy was defined as an error of fact in the radiology report, which led to incorrect management or patient harm. RESULTS: Registrars have higher DR than consultants (6.86% versus 2.77%). The major DR for consultants met national standards (<5%). The major DRs for registrars met the national audit standard (<10%), but not the National Emergency Laparotomy Audit (NELA) standard (<5%). When comparing between reporter subgroups, gastrointestinal (GI) radiologists have a lower major DR than general radiologists (1.22% versus 3.44%). GI radiologists were also found to correct more registrar provisional reports. The existence of a documented preoperative discussion between radiologists and surgeons was associated with a lower DR. CONCLUSIONS: DR for registrars and consultants are below the national audit standard. Several factors associated with a lower DR in acute abdominopelvic CT were also identified, including reporting by consultants, reporting by GI radiologists and preoperative discussions between the radiologist and surgeon.

Can subcentimetre ultrasound detected angiomyolipomas be safely disregarded?

AIM: To optimise follow-up by dismissing lesions on baseline ultrasound (US) if renal lesions conform to US criteria of an angiomyolipoma (AML). METHOD AND MATERIALS: The present study was a 10-year retrospective review of patients who were found to have incidental hyperechoic renal lesions on US to ascertain the outcome from subsequent imaging, clinical encounters, and cancer registrations. Exclusions included renal calculi, tuberous sclerosis, Von-Hippel-Lindau, or a known cancer. RESULTS: After excluding 39 patients, 1,493 patients were identified. One hundred and sixty had more than one lesion with 87 patients having bilateral lesions. Regardless of indication, 889 patients had subsequent imaging within 5 years (59.5%). The average size of all AMLs was 13.2 mm. In the group with lesions that were <10 mm (807), 438 had imaging follow-up with an average follow-up time of 1.5 years. Mean lesion size in this group was 7 mm, with an average increase of <0.5 mm on follow-up. No lesions were found to be malignant on subsequent imaging nor did any of these patients have a subsequent renal cancer diagnosis registered at local multidisciplinary team meetings. CONCLUSION: No incidental subcentimetre hyperechoic renal lesion with imaging characteristics of an AML demonstrated significant growth or developed into a malignancy on follow-up.

Predictors for 30-day mortality and complications following radiologically inserted gastrostomies: a single centre, large cohort review.

AIM: To measure the 30-day mortality and delayed complication rates following radiologically inserted gastrostomy (RIG) placement and determine the predictive risk factors for 30-day mortality and delayed complications to aide pre-procedure informed consent. MATERIALS AND METHODS: Retrospective analysis was undertaken of RIG insertions between July 2012 and August 2017 at a single tertiary centre, which included 373 patients (56% male; median age: 65 years, range: 19-92 years). Data were collected from electronic databases on patient demographics, RIG indication, all-cause mortality, complication rates, patient co-morbidities, and biochemical/haematological parameters. Multivariate analysis was performed to identify predictive risk factors for complications and mortality. RESULTS: The RIG procedural success rate was 97.9%. The overall 30-day mortality rate was 7.8%; associated with pre-procedural haemoglobin <130 g/l in men (p=0.030, odds ratio [OR] 23.38), white cell count >11×109/l (p=0.001, OR 4.18), C-reactive protein >10 mg/l (p=0.003, OR 10.10) and international normalised ratio (INR) >1.2 (p=0.03, OR 4.63). Inpatient RIG referrals were associated with 10% 30-day mortality; compared to 1.1% for outpatients (p=0.028, OR 9.51). The incidence of immediate and delayed complications was 2.4% and 42.1%, respectively. Neuromuscular disease was associated with gastrostomy dislodgement (p=0.0001, OR 4.99) and fracture (p=0.0009, OR 13.45), cerebrovascular disease with gastrostomy dislodgement (p=0.009, OR 2.51), cardiovascular disease with sepsis 30-days post-RIG (p=0.02, OR 2.94), and diabetes mellitus with gastrostomy dislodgement (p=0.0001, OR 29.45), fracture (p=0.027, OR 5.63) and stoma site infections (p=0.0003, OR 7.16). CONCLUSION: RIG 30-day mortality was significantly associated with inpatient procedures compared to outpatient, and a range of biochemical/haematological parameters that suggest infection pre-intervention. It is advised that the markers of infection and catabolism are investigated pre-intervention, which may reduce mortality and complication rates.

Optimising MRI small bowel techniques.

Magnetic resonance imaging (MRI)-based techniques have emerged as the preferred technique for the diagnostic evaluation of the small intestine, particularly in the adult population. The lack of ionising radiation makes MRI ideal for use in younger patients or in cases that require repeated follow-up investigations. Imaging of the small intestine may be carried out using the intubation (enteroclysis) or the ingestion (enterography) techniques. Enterography examinations are more acceptable to patients and may provide similar diagnostic accuracy compared to intubation methods. In this review, methods of improving and optimising MRI of the small intestine are described.

A retrospective review of registrar out-of-hours reporting in a university hospital: the effect of time and seniority on discrepancy rates.

AIM: To assess the influence of time, intensity, and trainee seniority on radiology registrars' major and minor discrepancy rates during weekend reporting at a university teaching hospital. MATERIALS AND METHODS: A 12-month retrospective review was performed of out-of-hours trainee provisional reports for computed tomography (CT) and magnetic resonance imaging (MRI) in a university teaching hospital. From Friday 9.00 pm to Sunday 9.00 pm, the out-of-hours service is provided by a single registrar rotating every 12 hours. A busy shift was defined as more than 24 reports issued during the shift. A senior trainee was defined as having more than 2 years' experience on the on-call rota. Reports were compared to subsequent subspecialist consultant review with all discrepancies collected. Discrepancy rates were calculated for junior/senior registrars, time of shift, and for busy/less busy shifts. RESULTS: The total discrepancy rate was 11.1%, with a major discrepancy rate of 3%. Junior registrars had a lower total discrepancy rate (9.7% versus 12.2%, p=0.0065). Although there was no difference between major discrepancies, junior trainees made fewer minor discrepancies (7.1% versus 8.93%, p=0.03). The discrepancy rate was higher at night (12.3% versus 10.4%, p=0.0418). On a less busy shift, more discrepancies were made (12.8% versus 10%, p=0.0001). CONCLUSION: The major discrepancy rate of trainees is low. More discrepancies are made at night, and trainee seniority does not mitigate this problem. Night shifts are less busy in comparison to day shifts, which may explain why less busy shifts appear to yield more mistakes.

Straight-to-test faecal tagging CT colonography for exclusion of colon cancer in symptomatic patients under the English 2-week-wait cancer investigation pathway: a service review.

AIM: To present the initial 12 months of data of a straight-to-test (STT) computed tomography colonography (CTC) protocol as the first-line investigation for change in bowel habit (CIBH) and iron deficiency anaemia (IDA) in patients over 60 referred directly from primary care. MATERIALS AND METHODS: In 12 months, 1,792 STT CTC for IDA and CIBH were performed. No colonoscopies were performed as the primary investigation in this cohort. Data from this cohort were gathered prospectively. RESULTS: The colorectal cancer (CRC) detection rate was 4.9% and polyp detection rate was 13.5%. The CRC rate increased related to age (p=0.001), the CRC detection rate was 2.6% in patients aged 60-69 years, compared to 4.9%, 7.4%, and 11.4% in the 70-79, 80-89, and >90 years age groups. The CRC rate was higher in patients with IDA compared to CIBH (6.8% versus 3.9%, p=0.017). There were significantly more left-sided cancers (p=0.0165). Non-colonic cancers were found in 4.3% of patients and 6.8% had incidental findings that required further investigation and 11.9% had a new, potentially significant, incidental finding. CONCLUSION: These results are comparable to colonoscopy in terms of diagnostic accuracy and similar to those of CTC in published multicentre trials. This exciting model of care within radiology enables earlier testing, reduces waiting times, with fewer outpatient appointments, and results in good clinician and patient satisfaction.

Assessment of the inferior mesenteric vein diameter as a surrogate marker to evaluate response to neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma.

AIM: Neoadjuvant chemoradiotherapy for locally advanced rectal cancer aims to downstage prior to definitive management. Repeat imaging assessment of the tumour post-therapy has implications for treatment. Our aim was to assess if the inferior mesenteric vein (IMV) diameter measured on CT can be used as a surrogate marker for evaluation of tumour response to neoadjuvant treatment. METHOD: IMV diameter was assessed in patients with and without locally advanced rectal cancer, pre- and post-radiotherapy, to ascertain if IMV diameter is a surrogate marker of tumour response. RESULTS: IMV diameter was 5.9 mm in patients with rectal cancer vs 4.7 mm in patients without (P = 0.0001). The baseline IMV diameter was significantly higher for cases with local lymphadenopathy [N0 5.2 mm vs N1/2 6 mm (P = 0.0059)] and extramural venous invasion (EMVI) [negative 5.4 mm vs positive 6.4 mm (P = 0.0001)]. Post-radiotherapy there was a significant decrease in the IMV diameter in cases with treatment response compared to non-responders: the percentage change in IMV diameter was a 17.54% decrease vs 1.39% increase (P = 0.0001). These results were reproduced on comparing between magnetic resonance tumour regression grades using ANOVA (P = 0.0001). There was also a significant decrease in IMV diameter when assessing lymph node (LN) and EMVI response vs non-responders (P = 0.0001 and 0.0001 respectively). CONCLUSION: Patients with rectal cancer have a dilated IMV compared with patients without rectal cancer. We confirm that IMV diameter is a potential surrogate marker of LN status and EMVI at baseline. IMV diameter is also a marker of tumour, LN and EMVI response to chemoradiotherapy.

Minimising the impact of errors in the interpretation of CT images for surveillance and evaluation of therapy in cancer.

Radiological error is inevitable and usually multifactorial. Error can be secondary to radiologist-specific causes, including cognitive and perceptive errors or ambiguity of report, or system-related causes, including inadequate, misleading, or incorrect clinical information, poor imaging technique, excessive workload, and poor working conditions. In this paper, we discuss a systematic approach to reduce errors in oncological radiology reporting, thus reducing risk to the patient. Rather than attempt to discuss all types of error, we concentrate on the most important and commonly occurring errors that we have encountered over 20 years of practice, based on weekly discrepancy reviews of our practice and independent reviews of clinical and research imaging from other institutions. This review focuses on computed tomography (CT) reporting for staging, surveillance, and response assessment of cancer patients, but the messages apply to all imaging methods.

Investigation of unprovoked venous thromboembolism: a case for a tempered approach?

AIM: To investigate and review the diagnostic yield for occult malignancy in patients who underwent abdominopelvic computed tomography (CT) after the diagnosis of unprovoked venous thromboembolism (VTE) with reference to the guidelines set by The National Institute for Health and Clinical Excellence (NICE). MATERIALS AND METHODS: We retrospectively reviewed all unprovoked VTE diagnosed within a large teaching hospital over a period of 21 months for subsequent imaging investigations and cancer diagnoses. The primary outcome was confirmed cancer diagnosis; patients were followed for a minimum of 12 months. RESULTS: Three hundred and five unprovoked VTEs were diagnosed in the study period, 31% of all VTEs. Of this cohort, 73.1% underwent further imaging for exclusion of occult malignancy. Fifteen (4.9%) cancers were diagnosed; with no subsequent malignancy reported in a 12-month follow-up period of the remaining 290 patients. Of the 15 cancers, seven were post-pulmonary emboli, all of which were identified on the initial CT pulmonary angiogram, thus abdominopelvic CT only was used to locate the primary and to undertake staging. Eight were post-deep-vein thrombosis (DVT). Thus the diagnostic yield for malignancy on abdominopelvic CT post-unprovoked VTE was 2.3%. The majority of diagnosed cancers were advanced with 80% dying in the follow-up period with a mean survival of 3.4 months. CONCLUSION: The pick-up rate of occult malignancy on abdominopelvic CT post-unprovoked VTE in the present study was 2.3%, far less than the generally quoted rate of 10%; however, similar to other rates in the literature. The benefit abdominopelvic CT brings to the diagnosis of occult malignancy post-unprovoked VTE is irresolute.

Imaging protocol for suspected ureteric calculi in patients presenting to the emergency department.

AIM: To ensure diagnostic yields were adequate in patients with suspected ureteric calculi with and without haematuria, and to assess whether there was a significant difference between these two groups in men and women. MATERIALS AND METHODS: A retrospective analysis was undertaken of 513 patient records who attended the Emergency Department with suspected ureteric colic over 8 months. RESULTS: 513 patient records were evaluated. The overall positive rate for calculi was 45.4%, with an alternative diagnosis in 14.4%. Of the patients scanned with haematuria 49.36% were positive. The positive scan rate in males was significantly higher than in females (56% v. 31%, p < 0.0001). 32.79% of patients scanned without haematuria had a proven calculus. The positive rate in males without haematuria was 40.39% versus 27.14% in females. CONCLUSION: The overall diagnostic yield of 45.4% is acceptable according to national guidelines. A large number of patients scanned without haematuria were found to have a calculus. This review suggests that in males a negative urine dipstick should not preclude CT investigation for renal colic in the presence of a "classical" history. However, the number of female patients with negative scans suggests that further randomized studies are needed to identify the ideal investigation pathway in women.

Intravenous omega-3 fatty acids are associated with better clinical outcome and less inflammation in patients with predicted severe acute pancreatitis: A randomised double blind controlled trial.

BACKGROUND AND AIMS: Omega-3 fatty acids (FA) can ameliorate the hyper-inflammatory response that occurs in conditions such as severe acute pancreatitis (SAP) and this may improve clinical outcome. We tested the hypothesis that parenteral omega-3 FA from a lipid emulsion that includes fish oil could be beneficial in patients with predicted SAP by reducing C-reactive protein (CRP) concentration (primary outcome), and modulating the inflammatory response and improving clinical outcome (secondary outcomes). METHODS: In a phase II randomized double-blind single-centre controlled trial, patients with predicted SAP were randomised to receive a daily infusion of fish oil containing lipid emulsion (Lipidem® 20%, BBraun) for 7 days (n = 23) or a daily infusion of a lipid emulsion without fish oil (Lipofundin® MCT 20%, BBraun) (n = 22). RESULTS: On admission, both groups had comparable pancreatitis predicted severity and APACHE II scores. Administration of fish oil resulted in lower total blood leukocyte number (P = 0.04), CRP (P = 0.013), interleukin-8 (P = 0.05) and intercellular adhesion molecule 1 (P = 0.01) concentrations, multiple organ dysfunction score, sequential organ failure assessment score (P = 0.004), early warning score (P = 0.01), and systemic inflammatory response syndrome (P = 0.03) compared to the control group. The fish oil group had fewer new organ failures (P = 0.07), lower critical care admission rate (P = 0.06), shorter critical care stay (P = 0.03) and shorter total hospital stay (P = 0.04). CONCLUSIONS: It is concluded that intravenous administration of a fish oil containing lipid emulsion, a source of omega-3 FA, improves clinical outcomes in patients with predicted SAP, benefits that may be linked to reduced inflammation. CLINICALTRIALS. GOV NUMBER: NCT01745861. EU CLINICAL TRIALS REGISTER: EudraCT (2010-018660-16).

Prediction of mortality in adult emergency department patients with sepsis.

OBJECTIVES: To determine the efficacy of the abbreviated Mortality in Emergency Department Sepsis (MEDS) score, the Modified Early Warning (MEW) score and near-patient-test (NPT) lactate levels in predicting 28-day mortality in adult emergency department (ED) patients with sepsis. METHODS: A retrospective cohort study of adult ED patients with sepsis admitted to hospital was conducted in a large urban teaching and a district general hospital. Data were collected during four time periods between 1 January 2006 and 31 January 2007. Inclusion criteria were age > or =16 years and an ED diagnosis of sepsis. Primary outcome for all patients was 28-day mortality. Patients were preassigned to risk groups according to their abbreviated MEDS score, MEW score and NPT lactate. RESULTS: 307 ED patients with sepsis were included in the study. Among these there were 72 deaths (23%). Mortality rates for the low-, moderate- and high-risk groups of the abbreviated MEDS score were 1/63 (1.6%), 48/205 (23.4%) and 23/39 (59.0%) patients. The MEDS score for low-risk patients was 98.6% (95% CI 92.5% to 99.9%) sensitive and 26.5% (95% CI 21.0% to 32.6%) specific and for high-risk patients it was 31.9% (95% CI 21.4% to 44.0%) sensitive and 93.2% (95% CI 89.2% to 96.1%) specific for death within 28 days. Mortality rates for the low- and high-risk MEW score were 20/159 (12.6%) and 52/148 (35.1%) patients. The MEW score for high-risk patients was 72.2% (95% CI 60.4% to 82.1%) sensitive and 59.2% (95% CI 52.6% to 65.5%) specific for mortality. An NPT lactate level of > or =4 mmol/l was 49.1% (95% CI 35.1% to 63.2%) sensitive and 74.3% (95% CI 64.8% to 82.3%) specific for 28-day mortality. CONCLUSION: These results demonstrate the efficacy of the abbreviated MEDS score, the MEW score and NPT venous lactate levels in predicting 28-day mortality in ED patients with sepsis. The abbreviated MEDS score was found to be the best performing risk assessment model which, with prospective validation, may aid early clinical decision-making in ED patients with sepsis and might affect the outcome from sepsis.

Phase I and pharmacokinetic trial of oral irinotecan administered daily for 5 days every 3 weeks in patients with solid tumors.

PURPOSE: We conducted a phase I dose-escalation trial of orally administered irinotecan (CPT-11) to characterize the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetic profile, and antitumor effects in patients with refractory malignancies. PATIENTS AND METHODS: CPT-11 solution for intravenous (IV) use was mixed with CranGrape juice (Ocean Spray, Lakeville-Middleboro, MA) and administered orally once per day for 5 days every 3 weeks to 28 patients. Starting dosages ranged from 20 to 100 mg/m2/d. RESULTS: Grade 4 delayed diarrhea was the DLT at the 80 mg/m2/d dosage in patients younger than 65 years of age and at the 66 mg/m2/d dosage in patients 65 or older. The other most clinically significant toxicity of oral CPT-11 was neutropenia. A linear relationship was found between dose, peak plasma concentration, and area under the concentration-time curve (AUC) for both CPT-11 and SN-38 lactone, implying no saturation in the conversion of irinotecan to SN-38. The mean metabolic ratio ([AUC(SN-38 total) + AUC(SN-38G total)]/AUC(CPT-11 total)) was 0.7 to 0.8, which suggests that oral dosing results in presystemic conversion of CPT-11 to SN-38. An average of 72% of SN-38 was maintained in the lactone form during the first 24 hours after drug administration. One patient with previously treated colorectal cancer and liver metastases who received oral CPT-11 at the 80 mg/m2/d dosage achieved a confirmed partial response. CONCLUSION: The MTD and recommended phase II dosage for oral CPT-11 is 66 mg/m2/d in patients younger than 65 years of age and 50 mg/m2/d in patients 65 or older, administered daily for 5 days every 3 weeks. The DLT of diarrhea is similar to that observed with IV administration of CPT-11. The biologic activity and favorable pharmacokinetic characteristics make oral administration of CPT-11 an attractive option for further clinical development.

Intra-abdominal focal fat infarction of the omentum: diagnosis and percutaneous management.

We present a case of a 68-year-old female who presented with left iliac fossa pain and postprandial vomiting for 7 days. Initial CT scan revealed a large mass within the upper abdomen in close proximity to the pancreatic tail, with central fat density, marginal enhancement, a distended vessel coursing through the centre and hazy increased density of the fat outside of the structure. A diagnosis of intra-abdominal focal fat infarction (IFFI) was made and she was treated conservatively. Subsequently, she re-presented with further pain and elevated inflammatory markers. A repeat CT scan again demonstrated the well-defined mass, but now with the development of fluid attenuation within the centre and several pockets of air. Radiologically guided percutaneous drains were inserted into the area of liquefaction and subsequent microbiology analysis revealed mixed coliform bacilli; targeted antibiotics were administered. The collection resolved on subsequent imaging. Identification of radiological features of IFFI is very helpful in establishing a diagnosis and may negate the need for surgical intervention.

Abdominopelvic irradiation for persistent advanced ovarian carcinoma.

The efficacy and toxicity of abdominopelvic irradiation following chemotherapy and positive second look laparotomy was assessed in 15 patients with advanced ovarian epithelial carcinoma. The patients received 30 Gy abdominal and 50.4 Gy pelvic irradiation. Three of ten patients with minimal disease are disease-free 30+, 72+, and 78+ months following therapy. A fourth patient survives disease-free 24+ months following third laparotomy. No patient with bulky disease is disease-free. Bowel obstruction was encountered in 5 of 15 patients; all episodes were associated with recurrent tumor. Abdominopelvic irradiation can potentially sterilize minimal volume ovarian carcinoma that persists following chemotherapy.

Excitatory amino acid projections to the nucleus accumbens septi in the rat: a retrograde transport study utilizing D[3H]aspartate and [3H]GABA.

Afferents to the nucleus accumbens septi utilizing glutamate or aspartate have been investigated in the rat by autoradiography following injection and retrograde transport of D[3H]aspartate. Parallel experiments with the intra-accumbal injection of [3H]GABA were employed to establish the transmitter-selective nature of the retrograde labelling found with D[3H]aspartate. The topography of cortical and thalamic perikarya labelled by D[3H]aspartate was extremely precise. D[3H]Aspartate labelled perikarya were found in layer V of agranular insular cortex; bilaterally within prelimbic and infralimbic subareas perikarya, but predominantly ipsilaterally. Ipsilateral labelling was observed in dorsal, ventral and posterior agranular insular cortices, and in perirhinal cortex. Injections into ventral accumbens labelled perikarya in ipsilateral entorhinal cortex, while infusion of D[3H]aspartate into anterior caudate-putamen resulted in labelling of perikarya in ipsilateral cingulate and lateral precentral cortices. Following infusion of D[3H]aspartate, ipsilateral midline thalamic nuclei contained the highest density of labelled perikarya; infusions centred on nucleus accumbens resulted in heavy retrograde labelling of the parataenial nucleus, but labelling was sparse from a lateral site and not observed after injection into anterior caudate-putamen. Less prominent labelling of perikarya was seen in other thalamic nuclei (mediodorsal, central medial, rhomboid, reuniens and centrolateral), mostly near the midline. Perikaryal labelling was also found in the ipsilateral amygdaloid complex, particularly in basolateral and lateral nuclei. Only weak labelling resulted in ventral subiculum. Numerous labelled cells were present bilaterally in anterior olfactory nucleus, although perikarya were more prominent ipsilaterally. Labelled perikarya were not consistently observed in other regions (ventral tegmental area, medial substantia nigra, raphe nuclei and locus coeruleus) known to innervate nucleus accumbens. Presumptive anterograde labelling was detected in ventral pallidum/substantia innominata, ventral tegmental area and medial substantia nigra. [3H]GABA was generally not retrogradely transported to the same regions labelled by D[3H]aspartate; an exception being the anterior olfactory nucleus, where large numbers of labelled perikarya were found. [3H]GABA failed to label perikarya in thalamus and amygdala, and a topographic distribution of label was absent in neocortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Excitatory amino acid projections to the periaqueductal gray in the rat: a retrograde transport study utilizing D[3H]aspartate and [3H]GABA.

The afferents to the periaqueductal gray utilizing excitatory amino acid transmitters have been described in rat brain by autoradiography following microinfusion and retrograde transport of D[3H]aspartate. Parallel experiments employing injections of [3H]GABA established that the retrograde labelling found with D[3H]aspartate was transmitter-selective. Following infusion of D[3H]aspartate, perikaryal labelling was found in nine subcortical areas, particularly infralimbic and cingulate cortices, with a predominance of ipsilateral labelled perikarya. Heaviest cortical labelling was localized in perirhinal cortex, in an extensive band of cells adjoining the rhinal sulcus. The hypothalamus contained the heaviest perikaryal labelling within brain: D[3H]aspartate labelled cells in 11 hypothalamic and mammillary nuclei. Intense bilateral labelling was obtained in ventromedial hypothalamus, although the number of perikarya was lower contralaterally. D[3H]Aspartate also produced heavy ipsilateral labelling of perikarya in posterior hypothalamus. Labelling patterns in cortex and hypothalamus were precise and topographic, and [3H]GABA never labelled cells in these regions. Other telencephalic and diencephalic areas containing prominent, retrogradely labelled cells were the lateral septum, amygdala, zona incerta and lateral habenula. The relative density of labelled cells in mesencephalic areas was much lower than that found in cortex and hypothalamus, although D[3H]aspartate labelled a moderate number of perikarya in the inferior colliculus and cuneiform nucleus. A smaller number of heavily labelled cells was found in the parabrachial nuclei, Kolliker-Fuse nucleus and laterodorsal tegmental nucleus. Only occasional labelled perikarya were observed in the myencephalon. Low densities of labelled cells were found after the injection of [3H]GABA into the periaqueductal gray, and the only regions in which a small number of perikarya were labelled by both [3H]GABA and D[3H]aspartate were the dorsal raphe and parabrachial nuclei. Overall, the retrograde transport of D[3H]aspartate revealed a complex topographic and convergent network of afferent pathways to the periaqueductal gray likely to utilize an excitatory amino acid transmitter. Our findings confirm the selectivity of this neurochemical mapping technique and provide evidence that hypothalamic, habenular, subthalamic and cuneiform afferents to the periaqueductal gray utilize an acidic amino acid as their transmitter. They also confirm that corticofugal afferents to periaqueductal gray utilize an excitatory amino acid.