Avaliação Cintilográfica e Ecocardiográfica em Portadores de Variantes Patogênicas ou Provavelmente Patogênicas do Gene TTR sem Envolvimento Cardíaco Manifesto / Scintigraphic and Echocardiographic Study of Patients with Pathogenic or Probably Pathogenic Variants of the TTR Gene without Overt Cardiac Involvement

Resumo Fundamento: A amiloidose por transtirretina (ATTR) é uma doença infiltrativa causada pela deposição anormal de proteína principalmente no coração e no sistema nervoso periférico. Quando acomete o coração, a doença manifesta-se como uma cardiomiopatia restritiva e, quando afeta o sistema nervoso periférico e autônomo, apresenta-se como uma polineuropatia, podendo ser chamada de Polineuropatia Amiloidótica Familiar (PAF). Existem dois subtipos de ATTR, a ATTR selvagem, em que não há variantes genéticas, e a ATTR hereditária, caracterizada por uma variante no gene que codifica a proteína transtirretina (T/TR). Em ambos os subtipos, o envolvimento cardíaco é o principal marcador prognóstico. Objetivos: Avaliar a prevalência do envolvimento cardíaco subclínico em uma amostra de pacientes com variantes genéticas no gene TTR usando a cintilografia com pirofosfato e o ecocardiograma com strain; comparar os achados cintilográficos e as medidas de strain; avaliar a associação entre PAF e o envolvimento subclínico; e analisar se existe uma associação entre uma variante genética específica e o envolvimento cardíaco. Métodos: Estudo transversal com carreadores de variantes no gene TTR sem sintomas cardiovasculares e sem alterações nos parâmetros da eletrocardiografia ou do ecocardiograma convencional. Todos os pacientes foram submetidos à cintilografia com pirofosfato e à ecocardiografia com análise de strain. O envolvimento cardíaco subclínico, definido como um escore de Perugini ≥ 2, razão Coração (C)/ Hemitórax Contralateral (CL) ≥ 1,5 em uma hora, C/CL ≥ 1,3 na terceira hora, ou um strain longitudinal global (SGL) ≤ −17%. Realizadas análises descritiva e analítica, e aplicados o teste exato de Fisher e o teste de Mann-Whitney. Um valor de p<0,05 foi considerado significativo. Resultados: Os 23 pacientes avaliados apresentavam uma idade mediana de 51 (37-57) anos, 15 (65,2%) eram do sexo feminino, 12 (52,2%) eram pardos, nove (39,1%) apresentavam hipertensão arterial sistêmica, e nove (39,1%) tinham um diagnóstico prévio de PAF. Dos nove pacientes com PAF, oito (34,8%) usavam tafamidis. As variantes genéticas identificadas foram Val142IIe, Val50Met e IIe127Val. O valor mediano do SGL foi −19% (-16% - −20%). Dos 23 pacientes, nove (39,1%; 95% CI = 29-49%) preencheram os critérios de envolvimento cardíaco, seis (26%) somente pelo critério do SGL. Não houve associação entre PAF e um carreador assintomático avaliado por ecocardiograma com análise de strain e pela cintilografia com pirofostato (p=0,19). A prevalência de hipertensão arterial sistêmica, diabetes mellitus, dislipidemia, tabagismo e SGL reduzido não foi diferente entre os grupos. A velocidade da onda e' septal foi a única variável que apresentou diferença significativa entre os indivíduos com e sem SGL reduzido, com uma área sob a curva ROC de 0,80 (IC95% = 0,61-0,98, p = 0,027). A melhor acurácia diagnóstica foi alcançada com uma velocidade e' septal ≤ 8,5 cm/s. Não houve associação entre o tipo de variante genética e o envolvimento cardíaco pré-clínico, nem entre o uso de tafamidis e este mesmo envolvimento (37,5% versus 40,0%, p = 0,90). Conclusão: O envolvimento cardíaco subclínico foi frequente em uma amostra de carreadores da variante genética do gene TTR. Um valor do SGL reduzido foi o achado mais comum. Não houve associação entre a presença de polineuropatia amiloidótica e o envolvimento subclínico. O tipo de variante genética não foi associado com envolvimento cardíaco precoce. Nesta amostra, o uso de tafamidis (20mg/dia) não foi associado com uma menor prevalência de envolvimento cardíaco subclínico.

Abstract Background: Transthyretin amyloidosis (ATTR) is an infiltrative disease caused by abnormal protein deposition mainly in the heart and peripheral nervous system. When it affects the heart, the disease presents as restrictive cardiomyopathy; when it affects the peripheral and autonomic nervous system, it manifests as polyneuropathy, and is called familial amyloid polyneuropathy (FAP). There are two ATTR subtypes: wild-type ATTR, where there is no mutation, and mutant ATTR (ATTRm), which is characterized by a mutation in the gene encoding the transthyretin protein (TTR). In both subtypes, cardiac involvement is the major marker of poor prognosis. Objectives: To assess the prevalence of subclinical cardiac involvement in a sample of patients with TTR gene mutation by using pyrophosphate scintigraphy and strain echocardiography; to compare scintigraphy and strain findings; to evaluate the association between neurological manifestations (FAP) and subclinical cardiac involvement; and to analyze whether there is an association between any specific mutation and cardiac involvement. Methods: This is a cross-sectional study with carriers of the TTR gene mutation, without cardiovascular symptoms or changes in electrocardiographic or conventional echocardiographic parameters. All patients underwent pyrophosphate scintigraphy and strain echocardiography. Subclinical cardiac involvement was defined as a Perugini score ≥ 2, heart-to-contralateral lung (H/CL) ratio ≥ 1.5 at 1 h, H/CL ≥1.3 at 3 h, or global longitudinal strain (GLS) ≤ −17%. Descriptive and analytical analyses were performed and Fisher's exact test and Mann-Whitney test were applied. A value of p < 0.05 was considered significant. Results: The 23 patients evaluated had a median age of 51 years (IQR 37-57 years), 15 (65.2%) were female, 12 (52.2%) were Pardo, nine (39.1%) had systemic arterial hypertension, and nine (39.1%) had a previous diagnosis of FAP. Of the nine patients with FAP, 8 (34.8%) were on tafamidis. The associated mutations were Val142IIe, Val50Met, and IIe127Val. The median GLS in the sample was −19% (−16% to −20%). Of the 23 patients, nine (39.1%; 95% CI = 29-49%) met criteria for cardiac involvement, six (26%) by the GLS-based criteria only. There was no association between having FAP and being an asymptomatic carrier, as assessed by strain echocardiography and pyrophosphate scintigraphy (p = 0.19). The prevalence of systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, and reduced GLS did not differ between groups. Septal e' wave velocity was the only variable that significantly differed between individuals with and without reduced GLS, with an area under the ROC curve of 0.80 (95% CI = 0.61-0.98, p = 0.027). The best diagnostic accuracy was achieved with a septal e' velocity ≤ 8.5 cm/s. There was no association between mutation type and preclinical cardiac involvement, nor between tafamidis use and lower degree of cardiac involvement (37.5% versus 40.0%, p = 0.90). Conclusion: Subclinical cardiac involvement was common in a sample of TTR mutation carriers without cardiac involvement. Reduced left ventricular GLS was the most frequent finding. There was no association between the presence of amyloid polyneuropathy and subclinical cardiac involvement. Type of mutation was not associated with early cardiac involvement. In this sample, the use of tafamidis 20 mg/day was not associated with a lower prevalence of subclinical cardiac involvement.

The evaluation of maturity of heterotopic ossification by SPECT/CT fusion bone imaging / 实用放射学杂志

Objective To evaluate the maturity and metabolic status of heterotopic ossification(HO)by single-photon emission computed tomography(SPECT)/CT fusion bone imaging.Methods The clinical and SPECT/CT fusion bone imaging data of 57 patients with HO confirmed by pathology or follow-up were analyzed retrospectively.HO was graded by CT,and the characteristics of radioactive concentration of HO were analyzed.Results Of 57 cases,single lesion in 52 cases,and multiple lesions in 5 cases,with a total of 63 lesions,mostly located in the hip joint(55.6%,35/63)and thigh(19.0%,12/63).There were 41 lesions in the middle stage and 22 lesions in the late stage.In the visual evaluation of SPECT/CT fusion bone imaging,the middle stage lesions were mostly clumps or flakes,with moderate or high radioactive concentration(75.6%,31/41),furthermore,the concentration range was larger than or equal to the total or limited range of CT ossification(21/41,50.1%),with high concentration mainly located in the mixed areas of ossification density.The concentration of the late stage lesions was mostly non-radioactive(72.7%,16/22).Conclusion SPECT/CT fusion bone imaging can show the range,degree and maturity of HO radioactive concentration,and can accurately locate the area with osteoblastic activity,which provides scientific basis for the selection of surgical timing.

Effects of renal ROI and depth calibrated by 99Tc m-DMSA renal imaging on GFR measurement of the injured-kidney in infants with congenital hydronephrosis / 中华核医学与分子影像杂志

Objective:To investigate the application value of 99Tc m-dimercaptosuccinic acid (DMSA) renal static imaging to correct renal ROI and renal depth in measurement of glomerular filtration rate (GFR) of the injured-kidney in infants with congenital hydronephrosis. Methods:From January 2022 to November 2022, 30 infants with congenital hydronephrosis (25 males, 5 females, age 3.0(1.0, 5.5) months) in Nuclear Medicine Department of the Second Hospital of Shanxi Medical University were prospectively included. Sixty kidneys were divided into 3 groups according to the degree of hydronephrosis: normal group (7 left kidneys and 12 right kidneys), mild hydronephrosis group (10 left kidneys and 12 right kidneys) and moderate to severe hydronephrosis group (13 left kidneys and 6 right kidneys). The patients received 99Tc m-diethylenetriamine penta-acetic acid (DTPA) diuretic renal dynamic imaging and 99Tc m-DMSA renal static imaging within 3 days, and bilateral renal lateral acquisition was performed at the end of the imaging. The depths (cm) of kidneys measured based on the lateral image and Tonnesen′s formula were compared. The single kidney GFR (ml·min -1·1.73 m -2) measured after the renal ROI corrected, or renal depth corrected, or renal ROI-depth corrected by renal static imaging (aGFR single, dGFR single, adGFR single) was compared with that measured by Gates method (gGFR single). The one-way analysis of variance, the least significant difference- t test and Dunnett- t test were used for data analysis. Results:In different hydronephrosis groups, renal depths measured by dynamic imaging, static imaging and Tonnesen formulas were significantly different ( F values: 38.07-59.63, t values: 2.53-15.17, all P<0.05). There were no significant differences in renal depth between the two kinds of imaging in the normal group ( F values: 34.89, 54.30, both P<0.05; t values: 0.65, 1.60, both P>0.05). aGFR single of all groups were smaller than gGFR single, but the values were similar, and were not significantly different in normal kidneys ( F values: 3.02, 5.51, both P<0.05; t values: 0.12, 0.53, both P>0.05), while those in abnormal kidneys (left kidneys: 43.27±8.84 vs 46.19±7.88, F=9.75, t=2.18, both P<0.05; right kidneys: 39.87±10.25 vs 42.94±10.28, F=10.32, t=2.04, both P<0.05) and in mild (48.58±10.94 vs 51.08±11.44, F=10.34, t=2.04, both P<0.05), moderate to severe (34.41±8.84 vs 37.62±8.84, F=19.97, t=3.41, both P<0.05) hydronephrosis groups were different. The dGFR single was significantly higher than gGFR single in 3 (normal, mild, moderate to severe) hydronephrosis groups ( t values: 3.82, 3.39, 3.81, all P<0.01). adGFR single was between aGFR single and dGFR single, and adGFR single were significantly different from gGFR single in normal right kidneys, in abnormal kidneys and in mild and moderate to severe hydronephrosis groups ( t values: 2.25-3.12, all P<0.05). Conclusions:Renal static imaging corrected ROI can improve the accuracy of GFR measurement of the affected kidney, especially for children with moderate and severe congenital hydronephrosis. However, the GFR corrected for renal depth or ROI-depth are significantly different from the true GFR. The lateral kidney depth measured by static imaging is more accurate than that measured by dynamic imaging.

Clinical applications and progress of radionuclide imaging in neuroblastoma / 中华核医学与分子影像杂志

Neuroblastoma is the most common extracranial solid tumor in children. The prognosis of different stages varies greatly, and its risk staging system is completely based on imaging. Radionuclide imaging plays an important role in the diagnosis and staging of various tumors, and it is also of great significance in the early diagnosis and staging of neuroblastoma. At present, imaging agents used for neuroblastoma mainly include catecholamine receptor, glucose metabolism, somatostatin receptor, etc. This article mainly discusses the application value and research progress of these imaging agents in the diagnosis of neuroblastoma.

Radiotheranostics:Challenges and opportunities / 中国医学影像技术

The radiotheranostics allows for precise diagnosis and treatment of differentiated thyroid cancer,neuroendocrine tumors,prostate cancer and other malignant diseases through providing solutions for personalized medicine.The development of radiotheranostics owns opportunities but also confronts challenges,including developing novel radiopharmaceuticals with new targets,clinical translation,radiometry and safety assessment.The challenges and opportunities of radiotheranostics were looked in this article.

Clinical research progresses of radiotheranostics in diagnosis and therapy of diseases / 中国医学影像技术

Combining with molecular imaging,nuclear medicine gradually utilized radiopharmaceuticals with targeted radionuclide therapy for accurate diagnosis and individualized treatment of diseases,hence advancing the progresses of theranostics.The clinical research progresses of radiotheranostics in diagnosis and therapy of diseases were reviewed in this article.

Progress in Cardiac Neuroreceptor Imaging in Parkinson's Disease / 中国医学影像学杂志

Parkinson's disease(PD),as a neurodegenerative disorder,is often accompanied by dysfunction of the cardiac autonomic nervous system.Clinical manifestations include arrhythmias,blood pressure fluctuations,pacemaker dependency,and abnormalities in cardiac valve function.These changes can have a significant impact on the quality of life and prognosis of patients.Therefore,early detection and monitoring of cardiac autonomic dysfunction in PD patients is crucial and can provide appropriate treatment and management strategies to alleviate cardiac symptoms and risks.Cardiac sympathetic nerve receptor imaging is a method that can visually display the integrity and functional status of the cardiac sympathetic nervous system.It has high sensitivity for evaluating cardiac sympathetic nerve function,which is essential for early diagnosis of PD.This article focuses on the latest research progress in the use of cardiac sympathetic nerve receptor imaging agents for PD diagnosis.

Application and progress of 99Tc m-GSA and 99Tc m-mebrofenin hepatobiliary scintigraphy in liver reserve function assessment / 中华核医学与分子影像杂志

The liver reserve function refers to the compensatory ability to maintain liver function after damage, providing implication for the resection of hepatic malignant tumor. Hepatobiliary scintigraphy imaging can provide quantitative evaluation of liver blood perfusion, and has advantages on the evaluation of liver reserve function and the prediction of postoperative complications. 99Tc m-galactosyl serum albumin (GSA) and 99Tc m-mebrofenin are commonly used imaging agents for hepatobiliary scintigraphy imaging assessment of liver reserve function. This article reviews the application and progress of hepatobiliary scintigraphy in liver reserve function assessment.

Application of diuretic renal scintigraphy in the treatment of infants with severe hydronephrosis / 中华核医学与分子影像杂志

Objective:To explore the differences of renal dynamic imaging parameters between operation group and non-operation group in infants with severe hydronephrosis, so as to accumulate theoretical basis for diuretic renal scintigraphy to help the treatment decision making.Methods:A total of 107 infants (age: 3(2, 6) months; 90 males and 17 females) with severe hydronephrosis, who underwent diuretic renal scintigraphy between March 2018 and October 2021 in Shanxi Children′s Hospital were retrospectively reviewed. All patients were diagnosed with ureteropelvic junction obstruction and divided into operation group ( n=87) and no-operation group ( n=20). The differences of differential renal function (DRF), peak time, half-time and drainage curve between the two groups were compared with the independent-sample t test or χ2 test, and the correlation between the renal function of the affected side and the anteroposterior pelvic diameter (APD) was analyzed with Pearson correlation analysis. Results:The operation group included 17 patients with DRF<40%, 60 patients with DRF between 40%-55%, and 10 patients with DRF>55%(supernormal renal function). The 40%-55% was considered as normal DBF, and the rest were abnormal. Infants with abnormal renal function in the operation group ( n=27) were more than those in the non-operation group ( n=3), but there was no statistical difference ( χ2=2.07, P=0.150). The proportion of obstruction curve in the operation group (85.1%, 74/87) was significantly higher than that in the non-operation group (55.0%, 11/20; χ2=7.24, P=0.007). Compared with the non-operation group, the peak time of affected kidney in the operation group was significantly longer ((22.77±7.52) vs (15.26±10.29) min; t=3.78, P<0.001), as well as the peak time of contralateral kidney ((11.25±8.47) vs (6.65±5.75) min; t=2.30, P=0.023). There was a negative correlation between the DRF of the affected side and the APD ( r=-0.48, P<0.001). Conclusions:The DBF is mostly in the normal range in infants with severe hydronephrosis, and supernormal renal function is common. The previous operation indication (DRF<40%) is not suitable for the infants, and it needs to be analyzed combined with the type of curve and the APD determined by color Doppler ultrasound. The prolongation of contralateral renal peak time may be an important parameter for the surgical evaluation of severe hydronephrosis in infants.

Preliminary study on the ability of 68Ga-Pentixafor PET/CT to differentiate between adrenal aldosterone-producing adenoma and nonfunctional adenoma / 中华内科杂志

Objective:To evaluate the ability of 68Ga-Pentixafor (nuclide ligand imaging agents for chemokine receptor 4) PET/CT to differentiate between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), and to assess how well this imaging method correlates with clinical features and postoperative outcomes. Methods:This was a cross-sectional study involving 73 APA and 12 NFA patients who received 68Ga-Pentixafor PET/CT imaging at Peking Union Medical College Hospital from August 2018 to October 2021. The receiver operating characteristic (ROC) curve was used to evaluate the differential value of visual analysis and the maximum standard uptake value (SUV max) of the focus on APA and NFA. The related factors of SUV max, and its predictive effect on postoperative outcomes were analyzed using Pearson or Spearman analysis and χ2 text. Results:68Ga-Pentixafor PET/CT imaging was positive in 64 APA patients (sensitivity=87.7%) and negative in all 12 NFA patients (specificity=100%). The area under the ROC curve with SUV max differentiating APA and NFA was 0.932 ( P<0.001). When the SUV max cut-off point was 6.23, the sensitivity was 80.8% and the specificity was 100%. The SUV max correlated positively with lesion size ( r=0.598) and aldosterone/renin activity ratio ( r=0.313) and correlated negatively with potassium level ( r=-0.286), renin activity ( r=-0.240) and age of diagnosis ( r=-0.273) (all P<0.05). Of the patients who underwent adrenalectomy and received more than 6 months of post-surgical follow-up, the clinical complete remission rate was higher for 68Ga-Pentixafor PET/CT imaging-positive patients than imaging-negative patients (24/39 vs. 0/4, P=0.031). Conclusions:68Ga-Pentixafor PET/CT is effective at differentiating between APA and NFA. The SUV max of 68Ga-Pentixafor PET/CT correlates with age at onset, lesion size, and the severity of clinical manifestations, and is able to predict postoperative outcomes.

Research progress in imaging manifestations and diagnosis and treatment of ectopic thyroid / 中国医师杂志

Ectopic thyroid (ETG) is a thyroid tissue located outside the normal anatomical position, often occurring in the chest. Clinical symptoms are related to its location and its impact on adjacent structures. In ETG imaging examination, single photon emission computed tomography (SPECT) nuclide imaging of thyroid perchlorate ( 99Tc mO 4-) is the most commonly used method for localization and characterization. ETG with normal function shows high radiation uptake in the corresponding area. For difficult to distinguish tumors in the base of the tongue and the thyrohyoid region, 131I or 123I imaging with more specificity for thyroid tissue uptake is needed. ETG exhibits a variety of manifestations in computed tomography (CT) and magnetic resonance imaging (MRI), mostly irregular soft tissue density masses with clear boundaries and uneven density. There are low-density cystic changes or high-density calcifications within the masses, with uneven or uniform enhancement. In ultrasound, ETG is mainly hypoechoic, with some showing cystic solid echoes and abundant blood flow signals within the gland. Asymptomatic ETG patients usually do not require treatment, while symptomatic patients often require surgical resection and have a good prognosis. Before surgery, relevant examinations should be combined to clarify the nature of the tumor as much as possible, to avoid permanent hypothyroidism caused by misdiagnosis and misresection.

Non-surgical management of vesicoureteral junction obstruction: a case report / Manejo não cirúrgico da obstrução da junção vesicoureteral: um relato de caso

Abstract Objective: To report the case of a pediatric patient with bilateral hydronephrosis due to vesicoureteral junction obstruction (VUJO) that was treated non-surgically and to discuss the approach of this anomaly. Case Description: A 25-month-old boy was referred without complaints for consultation due to prenatal ultrasound showing kidneys with cysts. He was under antibiotic prophylaxis. No family history of kidney disease and/or inherited disorders was reported. Renal ultrasound (RUS) at 2 days of life showed bilateral hydronephrosis, thus ruling out the possibility of kidney cystic disease. Dynamic renal scintigraphy (DTPA) showed marked retention of the marker in the pyelocaliceal system bilaterally, with little response to diuretic drug. He was maintained under antibiotic prophylaxis, when a new RUS showed bilateral ureteral dilatation, abrupt stenosis in the ureterovesical transition region (0.2 cm caliber), moderate bilateral hydronephrosis, and slight renal cortical thickness, confirming the diagnosis of VUJO. At 2 years and 10 months of age, DTPA showed hydronephrosis and ureteral stasis in both kidneys secondary to stenosis at the vesicoureteral junction (VUJ) level, with preservation of kidney function and slow degree of emptying. We opted for a non-surgical approach. RUS at 10 years of age showed significant improvement of all parameters, with ureteral transverse diameter of 9 mm, preserved VUJ, and age-appropriate bilateral kidney development. Comments: VUJO is a major cause of prenatal hydronephrosis and can trigger a deterioration of kidney function. Its treatment is still controversial but should take into account the importance of clinical follow-up and serial imaging evaluation.

Resumo Objetivo: Relatar o caso de um paciente pediátrico com hidronefrose bilateral devido à obstrução da junção vesicoureteral (OJVU) que foi tratado não cirurgicamente e discutir a abordagem desta anomalia. Descrição do caso: Um menino de 25 meses de idade foi encaminhado sem queixas para consulta devido à ultrassonografia pré-natal que mostrou rins com cistos. Ele estava sob profilaxia antibiótica. Nenhum histórico familiar de doença renal e/ou distúrbios hereditários foi relatado. A ultrassonografia renal (USR) aos 2 dias de vida mostrou hidronefrose bilateral, descartando assim a possibilidade de doença renal cística. A cintilografia renal dinâmica (DTPA) mostrou uma retenção acentuada do marcador no sistema pielocalicial bilateralmente, com pouca resposta ao diurético. O paciente foi mantido em profilaxia antibiótica, quando uma nova USR apresentou dilatação ureteral bilateral, estenose abrupta na região de transição ureterovesical (calibre 0,2 cm), hidronefrose bilateral moderada e leve espessura cortical renal, confirmando o diagnóstico de OJVU. Aos 2 anos e 10 meses de idade, a DTPA mostrou hidronefrose e estase ureteral em ambos os rins secundárias à estenose no nível da junção vesicoureteral (JVU), com preservação da função renal e grau lento de esvaziamento. Optamos por uma abordagem não cirúrgica. A USR aos 10 anos de idade mostrou melhora significativa de todos os parâmetros, com diâmetro transverso ureteral de 9 mm, JVU preservada, e desenvolvimento renal bilateral adequado à idade. Comentários: A OJVU é uma das principais causas de hidronefrose pré-natal e pode desencadear uma deterioração da função renal. Seu tratamento ainda é controverso, mas deve levar em consideração a importância do acompanhamento clínico e da avaliação seriada por imagem.

Reporte de un caso de tratamiento de gastroparesia pediátrica con prucaloprida: una terapia novedosa / A case report of prucalopride treatment in pediatric gastroparesis: a novel therapy

La prucaloprida acelera el vaciamiento gástrico en adultos con gastroparesia. No existen estudios con este medicamento en niños con gastroparesia. Se presenta un niño de 8 años que consultó por síntomas posprandiales de un mes de duración, con diagnóstico de gastroparesia por gammagrafía de vaciamiento gástrico. No mejoró con metoclopramida, domperidona, eritromicina y esomeprazol. Recibió prucaloprida durante dos períodos (durante 178 y 376 días) a dosis de 0,03-0,04 mg/kg/día. Presentó mejoría en el seguimiento con el índice cardinal de síntomas de gastroparesia y gammagrafías de vaciamiento gástrico. Por la buena respuesta, la prucaloprida podría ser una opción terapéutica en la gastroparesia pediátrica.

Prucalopride has been used in adults with gastroparesis, accelerating gastric emptying. There are no studies with this drug in gastroparetic children. An 8-year-old boy is presented who consulted for a month of postprandial symptoms, with a diagnosis of gastroparesis by gastric emptying scintigraphy. He did not improve with metoclopramide, domperidone, erythromycin, and esomeprazole. He received prucalopride for two periods (for 178 and 376 days) at doses: 0.03 - 0.04 mg/kg/day, presenting improvement in the follow-up with the cardinal gastroparesis symptom index and gastric emptying scintigraphy. Due to the good response, prucalopride may be a therapeutic option in pediatric gastroparesis.

68Ga-DOTATATE PET/CT versus 111In-octreotide scintigraphy in patients with neuroendocrine tumors: a prospective study / PET/CT com 68Ga-DOTATATE versus cintilografia com 111In-octreotide em pacientes com tumores neuroendócrinos: estudo prospectivo

Abstract Objective: To compare 68Ga-DOTA-DPhe1,Tyr3-octreotate (68Ga-DOTATATE) positron-emission tomography/computed tomography (PET/CT) findings with those of conventional 111In-octreotide scintigraphy in patients with neuroendocrine tumors (NETs). Materials and Methods: This was a single-center prospective study including 41 patients (25 males; mean age, 55.4 years) with biopsy-proven NETs who underwent whole-body 111In-octreotide scintigraphy and whole-body 68Ga-DOTATATE PET/CT. The patients had been referred for tumor staging (34.1%), tumor restaging (61.0%), or response evaluation (4.9%). Images were compared in a patient-by-patient analysis to identify additional lesions, and we attempted to determine the impact that discordant findings had on treatment planning. Results: Compared with 111In-octreotide scintigraphy, 68Ga-DOTATATE PET/CT revealed more lesions, the additional lesions typically being in the liver or bowel. Changes in management owing to the additional information provided by 68Ga-DOTATATE PET/CT occurred in five patients (12.2%), including intermodal changes in three (7.3%) and intramodal changes in two (4.9%). In addition, 68Ga-DOTATATE PET/CT yielded incidental findings unrelated to the primary NET in three patients (7.3%): Hürthle cell carcinoma of the thyroid, bowel non-Hodgkin lymphoma, and a suspicious breast lesion. Conclusion: We conclude that 68Ga-DOTATATE PET/CT is superior to conventional 111In-octreotide scintigraphy for the management of NETs because of its ability to determine the extent of the disease more accurately, which, in some cases, translates to changes in the treatment plan.

RESUMO Objetivo: Comparar os achados da PET/CT com 68Ga-DOTATATE em relação aos da cintilografia com 111In-octreotide em pacientes com tumores neuroendócrinos (TNEs). Materiais e Métodos: Estudo prospectivo unicêntrico incluindo 41 pacientes (25 homens; média de idade: 55,4 anos) com TNEs comprovados por biópsia submetidos a cintilografia de corpo inteiro com 111In-octreotide e PET/CT com 68Ga-DOTATATE. Os pacientes incluídos foram encaminhados para estadiamento do tumor (34,1%), reestadiamento (61,0%) ou avaliação da resposta (4,9%). As imagens foram comparadas para identificar lesões adicionais e o impacto dos achados discordantes no planejamento terapêutico. Resultados: Na comparação com a cintilografia com 111In-octreotide, a PET/CT com 68Ga-DOTATATE revelou mais lesões, mais frequentemente localizadas no fígado e intestino. Mudanças no tratamento devidas às informações adicionais reveladas pela PET/ CT ocorreram em 5/41 pacientes (12,2%), incluindo mudanças intermodalidade em três casos (7,3%) e intramodalidade em dois casos (4,9%). A PET/CT também identificou achados incidentais não relacionados ao TNE em 3/41 pacientes (7,3%), incluindo um carcinoma de células de Hürthle da tireoide, um linfoma não Hodgkin de intestino e uma lesão mamária suspeita. Conclusão: A PET/CT com 68Ga-DOTATATE é superior à cintilografia convencional com 111In-octreotide para o manejo de pacientes com TNEs, em virtude da sua capacidade de detectar a extensão da doença com mais precisão, o que se traduz, em alguns casos, em alterações terapêuticas.

Application value of delay-phase 99Tc m-PYP scintigraphy and SPECT imaging for diagnosis of transthyretin-related cardiac amyloidosis / 中华核医学与分子影像杂志

Objective:To investigate the application of different imaging methods of 99Tc m-pyrophosphate (PYP) in the diagnosis and pathological classification of cardiac amyloidosis (CA). Methods:A total of 31 patients (22 males, 9 females, age 21-81(57.2±13.4) years) with suspected CA who underwent 99Tc m-PYP dual-phase scintigraphy (early-phase: 1 h, delay-phase: 2-3 h) and SPECT/CT (1 h) between December 2018 and December 2019 in Peking Union Medical College Hospital were retrospectively included. Taking clinical diagnosis as the standard, the results of visual score (≥2, positive) and semi-quantitative values (heart to contralateral lung (H/CL)≥1.5, positive) of 99Tc m-PYP uptake in dual-phase scintigraphy and SPECT/CT imaging were analyzed. One-way analysis of variance and Bonferroni test were used to analyze the data. Results:Among 31 patients with suspected CA, 15 were clinically diagnosed as CA (5 patients with transthyretin-related CA (ATTR-CA) and 10 patients with light chain CA (AL-CA)) and 16 were diagnosed as non-CA. All 5 patients with ATTR-CA had positive dual-phase scintigraphy and SPECT/CT imaging results. Three out of 10 patients with AL-CA had positive early-phase scintigraphy whereas negative delay-phase scintigraphy and SPECT/CT imaging results. Sixteen patients who were clinically diagnosed as non-CA had negative dual-phase scintigraphy and SPECT/CT imaging results. The sensitivity (5/5), specificity (10/10), positive predictive value (5/5), negative predictive value (10/10) and accuracy (15/15) of delay-phase scintigraphy and SPECT/CT imaging were the same. Among 31 patients, 16 patients carried transthyretin-related (TTR) gene mutation, and 4 of them who clinically diagnosed as variant ATTR (ATTRv) had positive image findings while 12 of them who not clinically diagnosed as CA had negative image findings. There were significant differences in H/CL between ATTR-CA group and AL-CA group in early-phase (2.11±0.24 vs 1.31±0.07) and delay-phase (2.02±0.19 vs 1.30±0.05; F values: 75.41 and 87.15, Bonferroni test, both P<0.01). Conclusions:99Tc m-PYP delay-phase scintigraphy and SPECT/CT have high diagnostic efficiencies in ATTR-CA, helping to determine the pathological classification of CA; while early-phase scintigraphy has false positive results. Moreover, 99Tc m-PYP imaging is helpful to detect CA in patients with TTR gene mutation.

Automatic diagnosis and assessment of bone metastases on bone scans based on deep learning / 中华核医学与分子影像杂志

Objective:To develop an approach for the automatic diagnosis of bone metastasis and to design a parameter of quantitative evaluation for tumor burden on bone scans based on deep learning technology.Methods:A total of 621 cases (389 males, 232 females, age: 12-93 years) of bone scan images from the Department of Nuclear Medicine in Tenth People′s Hospital of Tongji University from March 2018 to July 2019 were retrospectively analyzed. Images were divided into bone metastasis group and non-bone metastasis group. Eighty percent of the cases were randomly extracted from both groups as the training set, and the rest of cases were used as the test set. A deep residual convolutional neural network ResNet34 was used to construct the classification model and the segmentation model. The sensitivity, specificity and accuracy were calculated and the performance differences of the classification model in different age groups (15 cases of <50 years, 75 cases of ≥50 and <70 years, 33 cases of ≥70 years) were analyzed. The regions of metastatic bone lesions were automatically segmented by the segmentation model. The Dice coefficient was used to evaluate the effect of the segmentation model and the manual labeled results. Finally, the bone scans tumor burden index (BSTBI) was calculated to assess the tumor burden of bone metastases.Results:There were 280 cases with bone metastases and 341 cases with non-bone metastases, including 498 in training set and 123 in test set. The classification model could accurately identify bone metastases, with the sensitivity, specificity and accuracy of 92.59%(50/54), 85.51%(59/69) and 88.62%(109/123), respectively, and it performed best in the <50 years group (sensitivity, 2/2; specificity, 12/13; accuracy, 14/15). The specificity in the ≥70 years group (8/12) was the lowest. The Dice coefficient of bone metastatic area and bladder area were 0.739 and 0.925 in the segmentation model, which performed similarly in the three age groups. Preliminary results showed that the value of BSTBI increased with the increase of the number of bone metastatic lesions and the degree of 99Tc m-MDP uptake. The machine learning model in this study took (0.48±0.07) s for the entire analysis process from input to the final BSTBI calculation. Conclusions:The deep learning based on automatic diagnosis framework for bone metastases can automatically and accurately identify segment bone metastases and calculate tumor burden. It provides a new way for the interpretation of bone scans. The proposed BSTBI may be used as a quantitative evaluation indicator in the future to assess the tumor burden of bone metastases based on bone scans.

Recombinant human thyroid-stimulating hormone for post-operative assessment in patients with low- to intermediate-risk differentiated thyroid cancer: results of phase Ⅰ study / 中华核医学与分子影像杂志

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Advances in the application of nuclear medicine imaging in the diagnosis and treatment of systematic light chain amyloidosis / 中华核医学与分子影像杂志

Systematic light chain (AL) amyloidosis is the most common forms of amyloidosis, which manifests as multiple organ system involvement, rapid progress, dire prognosis, difficult therapy and high mortality. Many patients may miss the optimal treatment as a result of not being diagnosed timely. Therefore, early diagnosis and assessment of involved extent of AL are clinical focuses. Related clinical studies have demonstrated that nuclear medicine imaging can be non-invasive in detecting amyloid deposits. It can not only early assess the extent and distribution of amyloid deposits in systemic AL amyloidosis, but also offer the indications for risk stratification, treatment response monitoring and prognosis assessment of the patients, especially for positron amyloidosis-specific tracers, which may have great prospects in the future. This review summarizes the application of nuclear medicine imaging in the systematic AL amyloidosis.

Imaging features of 99Tc m-dextran lymphoscitigraphy in thoracic duct exports obstruction / 中华核医学与分子影像杂志

Objective:To compare the 99Tc m-dextran(DX) lymphoscitigraphy and direct lymphography (DLG), in order to investigate the imaging features and clinical significance of 99Tc m-DX lymphoscitigraphy in patients with thoracic duct exports (TDE)obstruction. Methods:A total of 304 patients (140 males, 164 females, median age: 32 years) with TDE obstruction confirmed by thoracic duct exploration between 2017-01-01 and 2019-01-01 in Beijing Shijitan Hospital were retrospectively analyzed. Based on the different imaging characteristics of TDE, the reluts of 99Tc m-DX lymphoscitigraphy were divided into five groups (Ⅰ: no TDE presenting; Ⅱ: TDE presenting temporarily; Ⅲ: TDE presenting constantly or extensively; Ⅳ: abnormal reflux of imaging agents; Ⅴ: bilateral venous angle presenting). Ⅰ/Ⅱ groups were regarded as negative and Ⅲ-Ⅴ groups as positive. The consistency of 99Tc m-DX lymphoscitigraphy with DLG was evaluated with Kappa test, and the positive rates of the two methods were compared by McNemar test. Results:In the detection of TDE, the positive rate of 99Tc m-DX lymphoscintigraphy was 70.1% (213/304), which was significantly lower than that of DLG (97.4%, 296/304; χ2=4.16, P<0.001). The group Ⅲ has the largest number of cases (54.9%, 167/304), and there was a low consistency with DLG ( Kappa=0.08, P=0.005). However, there was a higher consistency between 99Tc m-DX lymphoscintigraphy results and the corresponding DLG results in the groups Ⅳ/Ⅴ ( Kappa values: 0.48, 0.86, both P<0.001). Furthermore, the diagnostic accordance rates of lower extremity lymphedema and chylous effusion were 96.1%(98/102) and 83.6%(127/152), respectively, compared with the clinical diagnosis. Conclusions:TDE obstruction of 99Tc m-DX lymphoscitigraphy presents in the majority with Ⅲ type. 99Tc m-DX lymphoscitigraphy results in patients with type Ⅳ and Ⅴ have a better consistency with those of DLG. 99Tc m-DX lymphoscitigraphy can be used as a screening tool of TDE obstruction, and play a role in the diagnosis of lower limb lymphedema and chylous effusion caused by TDE obstruction.